We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P=1 × 10⁻⁴) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10⁻⁷). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative condition characterized by progressive loss of upper and lower motor neurons, leading to death from respiratory failure in 70% of patients within 3 years of symptom onset. Although ALS is often described as a primarily motor-system disease, extramotor involvement occurs in up to 50% of cases, with prominent executive and behavioural impairment, and behavioural variant frontotemporal dementia (FTD) in up to 14% of cases¹. A neuropsychiatric prodrome has been described in some people with ALS–FTD, and higher rates of schizophrenia and suicide have been reported in first and second degree relatives of those with ALS, particularly in kindreds associated with the C9orf72 hexanucleotide repeat expansion². These clinical and epidemiological observations suggest that ALS and schizophrenia may share heritability.

ALS and schizophrenia both have high heritability estimates (0.65 and 0.64, respectively)^3,4; however the underlying genetic architectures of these heritable components appear to differ. Analysis of large genome-wide association study (GWAS) datasets has implicated over 100 independent risk loci for schizophrenia⁵ and estimated that a substantial proportion (23%) of the variance in underlying liability for schizophrenia is due to additive polygenic risk (many risk-increasing alleles of low individual effect combining to cause disease) conferred by common genetic variants⁶. This proportion, the single nucleotide polymorphism (SNP)-based heritability, is lower in ALS (8.2%), in which fewer than ten risk loci have been identified by GWAS⁷. Nevertheless, both diseases have polygenic components, but the extent to which they overlap has not been investigated.

Recently, methods to investigate overlap between polygenic traits using GWAS data have been developed^8,9,10. These methods assess either pleiotropy (identical genetic variants influencing both traits) or genetic correlation (identical alleles influencing both traits). Genetic correlation is related to heritability; for both measures, binary traits such as ALS and schizophrenia are typically modelled as extremes of an underlying continuous scale of liability to develop the trait. If two binary traits are genetically correlated, their liabilities covary, and this covariance is determined by both traits having identical risk alleles at overlapping risk loci. Studies of pleiotropy and genetic correlation have provided insights into the overlapping genetics of numerous traits and disorders, although none to date has implicated shared polygenic risk between neurodegenerative and neuropsychiatric disease. Here, we apply several techniques to identify and dissect the polygenic overlap between ALS and schizophrenia. We provide evidence for genetic correlation between the two disorders which is unlikely to be driven by diagnostic misclassification and we demonstrate a lack of polygenic overlap between ALS and other neuropsychiatric and neurological conditions, which could be due to limited power given the smaller cohort sizes for these studies.

Genetic correlation between ALS and schizophrenia

To investigate the polygenic overlap between ALS and schizophrenia, we used individual-level and summary data from GWAS for ALS⁷ (36,052 individuals) and schizophrenia⁵ (79,845 individuals). At least 5,582 control individuals were common to both datasets, but for some cohorts included in the schizophrenia dataset this could not be ascertained so this number is likely to be higher. For ALS, we used summary data from both mixed linear model association testing¹¹ and meta-analysis of cohort-level logistic regression¹². We first used linkage disequilibrium (LD) score regression with ALS and schizophrenia summary statistics; this technique models, for polygenic traits, a linear relationship between a SNP’s LD score (the amount of genetic variation that it captures) and its GWAS test statistic¹³. This distinguishes confounding from polygenicity in GWAS inflation and the regression coefficient can be used to estimate the SNP-based heritability (h_S²) for single traits¹³. In the bivariate case, the regression coefficient estimates genetic covariance (ρ_g) for pairs of traits, from which genetic correlation (r_g) is estimated⁸; these estimates are unaffected by sample overlap between traits. Using constrained intercept LD score regression with mixed linear model ALS summary statistics, we estimated the liability-scale SNP-based heritability of ALS to be 8.2% (95% confidence interval=7.2–9.1; mean χ²=1.13; all ranges reported below indicate 95% confidence intervals), replicating previous estimates based on alternative methods⁷. Estimates based on ALS meta-analysis summary statistics and free-intercept LD score regression with mixed linear model summary statistics were lower (Supplementary Table 1), resulting in higher genetic correlation estimates (Supplementary Table 2); for this reason, we conservatively use constrained intercept genetic correlation estimates for ALS mixed linear model summary statistics throughout the remainder of this paper. Heritability estimates for permuted ALS data were null (Supplementary Table 1).

LD score regression estimated the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P=1 × 10⁻⁴). Results were similar for a smaller schizophrenia cohort of European ancestry (21,856 individuals)¹⁴, indicating that the inclusion of individuals of Asian ancestry in the schizophrenia cohort did not bias this result (Supplementary Fig. 1). In addition to schizophrenia, we estimated genetic correlation with ALS using GWAS summary statistics for bipolar disorder¹⁵, major depressive disorder¹⁶, attention deficit-hyperactivity disorder¹⁷, autism spectrum disorder¹⁷, Alzheimer's disease (Supplementary Note 1)¹⁸, multiple sclerosis¹⁹ and adult height²⁰, finding no significant genetic correlation between ALS and any secondary trait other than schizophrenia (Fig. 1; Supplementary Table 2).

Error bars indicating 95% confidence intervals and P-values were calculated by the LD score regression software using a block jackknife procedure. Secondary traits are: AD, Alzheimer’s disease; ADHD, attention deficit-hyperactivity disorder; ASD, autism spectrum disorder; BPD, bipolar disorder; MDD, major depressive disorder; MS, multiple sclerosis; SCZ, schizophrenia.

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Polygenic risk score analysis

We supported the positive genetic correlation between ALS and schizophrenia by analysis of polygenic risk for schizophrenia in the ALS cohort. Polygenic risk scores (PRS) are per-individual scores based on the sum of alleles associated with one phenotype, weighted by their effect size, measured in an independent target sample of the same or a different phenotype¹⁰. PRS calculated on schizophrenia GWAS summary statistics for twelve P-value thresholds (P_T) explained up to 0.12% (P_T=0.2, P=8.4 × 10⁻⁷) of the phenotypic variance in a subset of the individual-level ALS genotype data that had all individuals removed that were known or suspected to be present in the schizophrenia cohort (Fig. 2; Supplementary Table 5). ALS cases had on average higher PRS for schizophrenia compared to healthy controls and harbouring a high schizophrenia PRS for P_T=0.2 significantly increased the odds of being an ALS patient in our cohort (Fig. 3; Supplementary Table 6). Permutation of case–control labels reduced the explained variance to values near zero (Supplementary Fig. 3).

P-value thresholds (P_T) for schizophrenia SNPs are shown on the x axis, where the number of SNPs increases with a more lenient P_T. Δ Explained variances (Nagelkerke R², shown as a %) of a generalized linear model including schizophrenia-based PRS versus a baseline model without polygenic scores (blue bars) are shown for each P_T. −Log₁₀ P-values of Δ explained variance per P_T (red dots) represent P-values from the binomial logistic regression of ALS phenotype on PRS, accounting for LD (Supplementary Table 4) and including sex and significant principal components as covariates (Supplementary Fig. 2). Values are provided in Supplementary Table 5.

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The figure applies to schizophrenia P-value threshold (P_T)=0.2. The PRS for this threshold were converted to ten deciles containing near identical numbers of individuals. Decile 1 contained the lowest scores and decile 10 contained the highest scores, where decile 1 was the reference and deciles 2–10 were dummy variables to contrast to decile 1 for OR calculation. The case:control ratio per decile is indicated with grey bars. Error bars indicate 95% confidence intervals. Significant differences from decile 1 were determined by logistic regression of ALS phenotype on PRS decile, including sex and principal components as covariates and are indicated by *P<0.05 or ***P<0.001.

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Modelling misdiagnosis and comorbidity

Using BUHMBOX²¹, a tool that distinguishes true genetic relationships between diseases (pleiotropy) from spurious relationships resulting from heterogeneous mixing of disease cohorts, we determined that misdiagnosed cases in the schizophrenia cohort (for example, young-onset FTD–ALS) did not drive the genetic correlation estimate between ALS and schizophrenia (P=0.94). Assuming a true genetic correlation of 0%, we estimated the required rate of misdiagnosis of ALS as schizophrenia to be 4.86% (2.47–7.13) to obtain the genetic correlation estimate of 14.3% (7.05–21.6; Supplementary Table 7), which we consider to be too high to be likely. However, if ALS and schizophrenia are genetically correlated, more comorbidity would be expected than if the genetic correlation was 0%. Modelling our observed genetic correlation of 14.3% (7.05–21.6), we estimated the odds ratio for having above-threshold liability for ALS given above-threshold liability for schizophrenia to be 1.17 (1.08–1.26), and the same for schizophrenia given ALS (Supplementary Fig. 4). From a clinical perspective, to achieve 80% power to detect a significant (α=0.05) excess of schizophrenia in the ALS cohort as a result of this genetic correlation, the required population-based incident cohort size is 16,448 ALS patients (7,310–66,670).

Pleiotropic risk loci

We leveraged the genetic correlation between ALS and schizophrenia to discover novel ALS-associated genomic loci by conditional false discovery rate (cFDR) analysis^9,22 (Fig. 4; Supplementary Table 8). Five loci already known to be involved in ALS were identified (corresponding to MOBP, C9orf72, TBK1, SARM1 and UNC13A) along with five potential novel loci at cFDR<0.01 (CNTN6, TNIP1, PPP2R2D, NCKAP5L and ZNF295-AS1). No gene set was significantly enriched (after Bonferroni correction) in genome-wide cFDR values when analysed using MAGENTA.

Each point denotes a SNP; its x axis position corresponds to its chromosomal location and its height indicates the extent of association with ALS by cFDR analysis. The solid line indicates the threshold cFDR=0.01. Any gene whose role in ALS is already established is in bold. A complete list of all loci at cFDR⩽0.05 is provided in Supplementary Table 8.

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There is evolving clinical, epidemiological and biological evidence for an association between ALS and psychotic illness, particularly schizophrenia. Genetic evidence of overlap to date has been based primarily on individual genes showing Mendelian inheritance, in particular the C9orf72 hexanucleotide repeat expansion, which is associated with ALS and FTD, and with psychosis in relatives of ALS patients². In this study, we have replicated SNP-based heritability estimates for ALS and schizophrenia using GWAS summary statistics, and have for the first time demonstrated significant overlap between the polygenic components of both diseases, estimating the genetic correlation to be 14.3%. We have carefully controlled for confounding bias, including population stratification and shared control samples, and have shown through analysis of polygenic risk scores that the overlapping polygenic risk applies to SNPs that are modestly associated with both diseases. Given that our genetic correlation estimate relates to the polygenic components of ALS (h_S²=8.2%) and schizophrenia (h_S²=23%) and these estimates do not represent all heritability for both diseases, the accuracy of using schizophrenia-based PRS to predict ALS status in any patient is expected to be low (Nagelkerke’s R²=0.12% for P_T=0.2), although statistically significant (P=8.4 × 10⁻⁷). Nevertheless, the positive genetic correlation of 14.3% indicates that the direction of effect of risk-increasing and protective alleles is consistently aligned between ALS and schizophrenia, suggesting convergent biological mechanisms between the two diseases.

Although phenotypically heterogeneous, both ALS and schizophrenia are clinically recognizable as syndromes^23,24. The common biological mechanisms underlying the association between the two conditions are not well understood, but are likely associated with disruption of cortical networks. Schizophrenia is a polygenic neurodevelopmental disorder characterized by a combination of positive symptoms (hallucinations and delusions), negative symptoms (diminished motivation, blunted affect, reduction in spontaneous speech and poor social functioning) and impairment over a broad range of cognitive abilities²⁵. ALS is a late onset complex genetic disease characterized by a predominantly motor phenotype with recently recognized extra-motor features in 50% of patients, including cognitive impairment¹. It has been suggested that the functional effects of risk genes in schizophrenia converge by modulating synaptic plasticity, and influencing the development and stabilization of cortical microcircuitry⁵. In this context, our identification of CNTN6 (contactin 6, also known as NB-3, a neural adhesion protein important in axon development)²⁶ as a novel pleiotropy-informed ALS-associated locus supports neural network dysregulation as a potential convergent mechanism of disease in ALS and schizophrenia.

No significantly enriched biological pathway or ontological term was identified within genome-wide cFDR values using MAGENTA. Low inflation in ALS GWAS statistics, coupled with a rare variant genetic architecture⁷, render enrichment-based biological pathway analyses with current sample sizes challenging. Nevertheless, nine further loci were associated with ALS risk at cFDR <0.01. Of these, MOBP, C9orf72, TBK1, SARM1 and UNC13A have been described previously in ALS and were associated by cFDR analysis in this study owing to their strong association with ALS through GWAS⁷. The remaining four loci (TNIP1, PPP2R2D, NCKAP5L and ZNF295-AS1) are novel associations and may represent pleiotropic disease loci. TNIP1 encodes TNFAIP3 interacting protein 1 and is involved in autoimmunity and tissue homoeostasis²⁷. The protein product of PPP2R2D is a regulatory subunit of protein phosphatase 2 and has a role in PI3K-Akt signalling and mitosis²⁸. NCKAP5L is a homologue of NCKAP5, encoding NAP5, a proline-rich protein that has previously been implicated in schizophrenia, bipolar disorder and autism^29,30. ZNF295-AS1 is a noncoding RNA³¹. Further investigation into the biological roles of these genes may yield novel insight into the pathophysiology of certain subtypes of ALS and schizophrenia, and as whole-genome and exome datasets become available in the future for appropriately large ALS case–control cohorts, testing for burden of rare genetic variation across these genes will be particularly instructive, especially given the role that rare variants appear to play in the pathophysiology of ALS⁷.

Our data suggest that other neuropsychiatric conditions (bipolar disorder, autism and major depression) do not share polygenic risk with ALS. This finding contrasts with our recent observations from family aggregation studies and may be unexpected given the extensive genetic correlation between neuropsychiatric conditions⁶. This could relate to statistical power conferred by secondary phenotype cohort sizes, and future studies with larger sample sizes will shed further light on the relationship between ALS and neuropsychiatric disease. It is also possible that the current study underestimates genetic correlations due to the substantial role that rare variants play in the genetic architecture of ALS⁷ and future fine-grained studies examining heritability and genetic correlation in low-minor allele frequency and low-LD regions may identify a broader relationship between ALS and neuropsychiatric diseases.

A potential criticism of this study is that the polygenic overlap between ALS and schizophrenia could be driven by misdiagnosis, particularly in cases of ALS–FTD, which can present in later life as a psychotic illness and could be misdiagnosed as schizophrenia. This is unlikely, as strict diagnostic criteria are required for inclusion of samples in the schizophrenia GWAS dataset⁵. Furthermore, since core schizophrenia symptoms are usually diagnosed during late adolescence, a misdiagnosis of FTD-onset ALS–FTD as schizophrenia is unlikely. In this study, we found no evidence for misdiagnosis of ALS as schizophrenia (BUHMBOX P=0.94) and we estimated that a misdiagnosis of 4.86% of ALS cases would be required to spuriously observe a genetic correlation of 14.3%, which is not likely to occur in clinical practice. We are therefore confident that this genetic correlation estimate reflects a genuine polygenic overlap between the two diseases and is not a feature of cohort ascertainment, but the possibility of some misdiagnosis in either cohort cannot be entirely excluded based on available data.

A positive genetic correlation between ALS and schizophrenia predicts an excess of patients presenting with both diseases. Most neurologists and psychiatrists, however, will not readily acknowledge that these conditions co-occur frequently. Our genetic correlation estimate confers an odds ratio of 1.17 (1.08–1.26) for harbouring above-threshold liability for ALS given schizophrenia (or vice versa) and a lifetime risk of 1:34,336 for both phenotypes together. Thus, a very large incident cohort of 16,448 ALS patients (7,310–66,670), with detailed phenotype information, would be required to have sufficient power to detect an excess of schizophrenia within an ALS cohort. Coupled with reduced life expectancy in patients with schizophrenia³², this may explain the relative dearth of epidemiological studies to date providing clinical evidence of excess comorbidity. Moreover, it has also been proposed that prolonged use of antipsychotic medication may protect against developing all of the clinical features of ALS³³, which would reduce the rate of observed comorbidity. Considering our novel evidence for a genetic relationship between ALS and schizophrenia, this underscores the intriguing possibility that therapeutic strategies for each condition may be useful in the other, and our findings provide rationale to consider the biology of ALS and schizophrenia as related in future drug development studies. Indeed, the glutamate-modulating ALS therapy riluzole has shown efficacy as an adjunct to risperidone, an antipsychotic medication, in reducing the negative symptoms of schizophrenia³⁴.

In conclusion, we have estimated the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6), providing molecular genetic support for our epidemiological observation of psychiatric endophenotypes within ALS kindreds. To our knowledge, this is the first study to show genetic correlation derived from polygenic overlap between neurodegenerative and neuropsychiatric phenotypes. The presence of both apparent monogenic C9orf72-driven overlap² and polygenic overlap in the aetiology of ALS and schizophrenia suggests the presence of common biological processes, which may relate to disruption of cortical circuitry. As both ALS and schizophrenia are heterogeneous conditions, further genomic, biological and clinical studies are likely to yield novel insights into the pathological processes for both diseases and will provide clinical sub-stratification parameters that could drive novel drug development for both neurodegenerative and psychiatric conditions.

Study population and genetic data

For ALS, 7,740,343 SNPs genotyped in 12,577 ALS patients and 23,475 healthy controls of European ancestry organized in 27 platform- and country-defined strata were used⁷. The schizophrenia dataset comprised GWAS summary statistics for 9,444,230 SNPs originally genotyped in 34,241 patients and 45,604 controls of European and Asian ancestry⁵. For LD score regression, GWAS summary statistics were generated for the ALS cohort using mixed linear model association testing implemented in Genome-wide Complex Trait Analysis¹¹ or logistic regression combined with cross-stratum meta-analysis using METAL¹². To evaluate sample overlap for PRS and cFDR analyses, we also obtained individual-level genotype data for 27,647 schizophrenia cases and 33,675 controls from the schizophrenia GWAS (Psychiatric Genomics Consortium⁵ and dbGaP accession number phs000021.v3.p2). Using 88,971 LD-pruned (window size 200 SNPs; shift 20 SNPs; r²>0.25) SNPs in both datasets (INFO score>0.8; MAF>0.2), with SNPs in high-LD regions removed (Supplementary Table 4), samples were removed from the ALS dataset if they were duplicated or had a cryptically related counterpart (PLINK >0.1; 5,582 individuals) in the schizophrenia cohort and whole strata (representing Finnish and German samples; 3,811 individuals) were also removed if commonality with the schizophrenia cohort could not be ascertained (due to unavailability of individual-level genotype data in the schizophrenia cohort) and in which a sample overlap was suspected (Supplementary Table 3).

LD score regression

We calculated LD scores using LDSC v1.0.0 in 1 centiMorgan windows around 13,307,412 non-singleton variants genotyped in 379 European individuals (CEU, FIN, GBR, IBS and TSI populations) in the phase 1 integrated release of the 1,000 Genomes Project³⁵. For regression weights¹³, we restricted LD score calculation to SNPs included in both the GWAS summary statistics and HapMap phase 3; for r_g estimation in pairs of traits this was the intersection of SNPs for both traits and HapMap. Because population structure and confounding were highly controlled in the ALS summary statistics by the use of mixed linear model association tests, we constrained the LD score regression intercept to 1 for h_S² estimation in ALS, and we also estimated h_S² with a free intercept. For h_S² estimation in all other traits and for r_g estimation the intercept was a free parameter. We also estimated r_g using ALS meta-analysis results⁷ with free and constrained intercepts and with permuted data conserving population structure. Briefly, principal component analysis was carried out for each stratum using smartpca³⁶ and the three-dimensional space defined by principal components 1–3 was equally subdivided into 1,000 cubes. Within each cube, case–control labels were randomly swapped and association statistics were re-calculated for the entire stratum using logistic regression. Study-level P-values were then calculated using inverse variance weighted fixed effect meta-analysis implemented in METAL^7,12. h_S² was estimated for these meta-analysed permuted data using LD score regression (Supplementary Table 1).

Polygenic risk score analysis

We calculated PRS for 10,032 cases and 16,627 healthy controls in the ALS dataset (duplicate and suspected or confirmed related samples with the schizophrenia dataset removed), based on schizophrenia-associated alleles and effect sizes reported in the GWAS summary statistics for 6,843,674 SNPs included in both studies and in the phase 1 integrated release of the 1,000 Genomes Project³⁵ (imputation INFO score <0.3; minor allele frequency <0.01; A/T and G/C SNPs removed). SNPs were clumped in two rounds (physical distance threshold of 250 kb and a LD threshold (R²) of>0.5 in the first round and a distance of 5,000 kb and LD threshold of >0.2 in the second round) using PLINK v1.90b3y, removing high-LD regions (Supplementary Table 4), resulting in a final set of 496,548 SNPs for PRS calculations. Odds ratios for autosomal SNPs reported in the schizophrenia summary statistics were log-converted to beta values and PRS were calculated using PLINK’s score function for twelve schizophrenia GWAS P-value thresholds (P_T): 5 × 10⁻⁸, 5 × 10⁻⁷, 5 × 10⁻⁶, 5 × 10⁻⁵, 5 × 10⁻⁴, 5 × 10⁻³, 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5. A total of 100 principal components (PCs) were generated for the ALS sample using GCTA version 1.24.4. Using R version 3.2.2, a generalized linear model was applied to model the phenotype of individuals in the ALS dataset. PCs that had a significant effect on the phenotype (P<0.0005, Bonferroni-corrected for 100 PCs) were selected (PCs 1, 4, 5, 7, 8, 10, 11, 12, 14, 36, 49).

To estimate explained variance of PRS on the phenotype, a baseline linear relationship including only sex and significant PCs as variables was modelled first:

where y is the phenotype in the ALS dataset, α is the intercept of the model with a slope β for each variable x.

Subsequently, a linear model including polygenic scores for each schizophrenia P_T was calculated:

A Nagelkerke R² value was obtained for every model and the baseline Nagelkerke R² value was subtracted, resulting in a Δ explained variance that describes the contribution of schizophrenia-based PRS to the phenotype in the ALS dataset. PRS analysis was also performed in permuted case–control data (1,000 permutations, conserving case–control ratio) to assess whether the increased Δ explained variance was a true signal associated with phenotype. Δ explained variances and P-values were averaged across permutation analyses.

To ensure we did not over- or under-correct for population effects in our model, we tested the inclusion of up to a total of 30 PCs in the model, starting with the PC with the most significant effect on the ALS phenotype (Supplementary Fig. 2). Increasing the number of PCs initially had a large effect on the Δ explained variance, but this effect levelled out after 11 PCs. On the basis of this test we are confident that adding the 11 PCs that had a significant effect on the phenotype sufficiently accounted for possible confounding due to population differences.

For the schizophrenia P_T for which we obtained the highest Δ explained variance (0.2), we subdivided observed schizophrenia-based PRS in the ALS cohort into deciles and calculated the odds ratio for being an ALS case in each decile compared to the first decile using a similar generalized linear model:

Odds ratios and 95% confidence intervals for ALS were derived by calculating the exponential function of the beta estimate of the model for each of the deciles 2–10.

Diagnostic misclassification

To distinguish the contribution of misdiagnosis from true genetic pleiotropy we used BUHMBOX²¹ with 417 independent ALS risk alleles in a sample of 27,647 schizophrenia patients for which individual-level genotype data were available. We also estimated the required misdiagnosis rate M of FTD–ALS as schizophrenia that would lead to the observed genetic correlation estimate as C/(C+1), where C=ρ_gN_SCZ/N_ALS and N_SCZ and N_ALS are the number of cases in the schizophrenia and ALS datasets, respectively³⁷ (derived in Supplementary Methods 1).

Expected comorbidity

To investigate the expected comorbidity of ALS and schizophrenia given the observed genetic correlation, we modelled the distribution in liability for ALS and schizophrenia as a bivariate normal distribution with the liability-scale covariance determined by LD score regression (Supplementary Methods 2). Lifetime risks for ALS³⁸ and schizophrenia²⁵ of 1/400 and 1/100, respectively, were used to calculate liability thresholds above which individuals develop ALS or schizophrenia, or both. The expected proportions of individuals above these thresholds were used to calculate the odds ratio of developing ALS given schizophrenia, or vice versa (Supplementary Methods 2). The required population size to observe a significant excess of comorbidity was calculated using the binomial power equation.

Pleiotropy-informed risk loci for ALS

Using an adapted cFDR method⁹ that allows shared controls between cohorts²², we estimated per-SNP cFDR given LD score-corrected⁸ schizophrenia GWAS P-values for ALS mixed linear model summary statistics calculated in a dataset excluding Finnish and German cohorts (in which suspected control overlap could not be determined), but including all other overlapping samples (totalling 5,582). To correct for the relationship between LD and GWAS test statistics, schizophrenia summary statistics were residualized on LD score by subtracting the product of each SNP’s LD score and the univariate LD score regression coefficient for schizophrenia. cFDR values conditioned on these residualized schizophrenia GWAS P-values were calculated for mixed linear model association statistics calculated at 6,843,670 SNPs genotyped in 10,147 ALS cases and 22,094 controls. Pleiotropic genomic loci were considered statistically significant if cFDR<0.01 (following Andreassen et al.⁹) and were clumped with all neighbouring SNPs based on LD (r²>0.1) in the complete ALS dataset. Associated cFDR genomic regions were then mapped to the locations of known RefSeq transcripts in human genome build GRCh37. Genome-wide cFDR values were also tested for enrichment in 9,711 gene sets included in the MAGENTA software package (version 2.4, July 2011) and derived from databases such as Gene Ontology (GO, http://geneontology.org/), Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.kegg.jp/), Protein ANalysis THrough Evolutionary Relationships (PANTHER, http://www.pantherdb.org/) and INGENUITY (http://www.ingenuity.com/). SNPs were mapped to genes including 20 kb up- and downstream regions to include regulatory elements. The enrichment cutoff applied in our analysis was based on the 95th percentile of gene scores for all genes in the genome. The null distribution of gene scores for each gene set was based on 10,000 randomly sampled gene sets with equal size. MAGENTA uses a Mann–Whitney rank-sum test to assess gene-set enrichment³⁹.

Data availability

All data used in this study are publically available and can be accessed via the studies cited in the text. Other data are available from the authors upon reasonable request.

How to cite this article: McLaughlin, R. L. et al. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nat. Commun. 8, 14774 doi: 10.1038/ncomms14774 (2017).

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We acknowledge helpful contributions from Mr Gert Jan van de Vendel in the design and execution of PRS analyses. This study received support from the ALS Association; Fondation Thierry Latran; the Motor Neurone Disease Association of England, Wales and Northern Ireland; Science Foundation Ireland; Health Research Board (Ireland), The Netherlands ALS Foundation (Project MinE, to J.H.V., L.H.v.d.B.), the Netherlands Organisation for Health Research and Development (Vici scheme, L.H.v.d.B.) and ZonMW under the frame of E-Rare-2, the ERA Net for Research on Rare Diseases (PYRAMID). Research leading to these results has received funding from the European Community’s Health Seventh Framework Programme (FP7/2007–2013). A.G. is supported by the Research Foundation KU Leuven (C24/16/045). A.A.-C. received salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Samples used in this research were in part obtained from the UK National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. We acknowledge sample management undertaken by Biobanking Solutions funded by the Medical Research Council (MRC) at the Centre for Integrated Genomic Medical Research, University of Manchester. This is an EU Joint Programme-Neurodegenerative Disease Research (JPND) Project (STRENGTH, SOPHIA). In addition to those mentioned above, the project is supported through the following funding organizations under the aegis of JPND: UK, Economic and Social Research Council; Italy, Ministry of Health and Ministry of Education, University and Research; France, L’Agence nationale pour la recherche. The work leading up to this publication was funded by the European Community’s Health Seventh Framework Programme (FP7/2007–2013; Grant Agreement Number 2,59,867). We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i-Select chips was funded by the French National Foundation on Alzheimer's disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the MRC (Grant No. 5,03,480), Alzheimer’s Research UK (Grant No. 5,03,176), the Wellcome Trust (Grant No. 082604/2/07/Z) and German Federal Ministry of Education and Research: Competence Network Dementia Grant no. 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA Grant R01 AG033193 and the NIA AG081220 and AGES contract N01-AG-12,100, the NHLBI Grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA Grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association Grant ADGC-10–196728. The Project MinE GWAS Consortium included contributions from the PARALS registry, SLALOM group, SLAP registry, FALS Sequencing Consortium, SLAGEN Consortium and NNIPPS Study Group; the Schizophrenia Working Group of the Psychiatric Genomics Consortium included contributions from the Psychosis Endophenotypes International Consortium and Wellcome Trust Case–control Consortium. Members of these eight consortia are listed in Supplementary Note 2.

Author notes

1. • Russell L. McLaughlin
   •  & Dick Schijven

   These authors contributed equally to this work

2. • Jurjen J. Luykx
   • , Orla Hardiman
   •  & Jan H. Veldink

   These authors jointly supervised this work

Affiliations

1. Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin DO2 DK07, Republic of Ireland

   • Russell L. McLaughlin
   •  & Margaret O’Brien

2. Smurfit Institute of Genetics, Trinity College Dublin, Dublin D02 DK07, Republic of Ireland

   • Russell L. McLaughlin
   • , Daniel G. Bradley
   •  & Orla Hardiman

3. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands

   • Dick Schijven
   • , Wouter van Rheenen
   • , Kristel R. van Eijk
   • , Leonard H. van den Berg
   • , Jurjen J. Luykx
   • , Jan H. Veldink
   • , Annelot M. Dekker
   • , Frank P. Diekstra
   • , Rick A. A. van der Spek
   • , Perry T. C. van Doormaal
   •  & Michael A. van Es

4. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands

   • Dick Schijven
   • , René S. Kahn
   • , Roel A. Ophoff
   • , Jurjen J. Luykx
   • , Sara L. Pulit
   •  & Wiepke Cahn

5. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA

   • Roel A. Ophoff
   • , Martina Wiedau-Pazos
   •  & Rita M. Cantor

6. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90095, USA

   • Roel A. Ophoff
   • , Gerome Breen
   •  & Nelson B. Freimer

7. Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven—University of Leuven, Leuven B-3000, Belgium

   • An Goris

8. Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London WC2R 2LS, UK

   • Ammar Al-Chalabi
   • , Aleksey Shatunov
   • , William Sproviero
   • , Ashley R. Jones
   • , Isabella Fogh
   • , Kuang Lin
   • , Christopher E. Shaw
   • , Bradley N. Smith
   •  & John Powell

9. Department of Psychiatry, Hospital Network Antwerp (ZNA) Stuivenberg and Sint Erasmus, Antwerp 2020, Belgium

   • Jurjen J. Luykx

10. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia

    • Garth A. Nicholson
    • , Dominic B. Rowe
    • , Kelly Williams
    •  & Ian Blair

11. Concord Hospital, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia

    • Garth A. Nicholson

12. The Stacey MND Laboratory, Department of Pathology, The University of Sydney, Sydney, New South Wales, Australia

    • Roger Pamphlett

13. Brain and Mind Research Institute, The University of, Sydney, New South Wales, Australia

    • Matthew C. Kiernan

14. Transformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation, Sydney, New South Wales, Australia

    • Denis Bauer
    •  & Tim Kahlke

15. Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands

    • Filip Eftimov
    • , Anneke J. van der Kooi
    •  & Marianne de Visser

16. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy

    • Isabella Fogh
    • , Nicola Ticozzi
    • , Cinzia Tiloca
    • , Antonia Ratti
    •  & Vincenzo Silani

17. Department of Pathophysiology and Tranplantation, ‘Dino Ferrari’ Center, Università degli Studi di Milano, Milano, Italy

    • Nicola Ticozzi
    • , Antonia Ratti
    •  & Vincenzo Silani

18. Institut du Cerveau et de la Moelle épinière, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMRS1127, Paris, France

    • Stéphanie Millecamps

19. Ramsay Generale de Santé, Hopital Peupliers, Centre SLA Ile de France, Paris, France

    • François Salachas
    •  & Vincent Meininger

20. Institute of Physiology and Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal

    • Mamede de Carvalho
    •  & Susana Pinto

21. Department of Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal

    • Mamede de Carvalho
    •  & Susana Pinto

22. Department of Neurology, Hospital Carlos III, Madrid, Spain

    • Jesus S. Mora

23. Neurology Department, Hospital de la Santa Creu i Sant Pau de Barcelona, Autonomous University of Barcelona, Barcelona, Spain

    • Ricardo Rojas-García

24. Department Neurology and Emory ALS Center, Emory University School of Medicine, Atlanta, Georgia, USA

    • Meraida Polak
    •  & Jonathan Glass

25. Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, UK

    • Siddharthan Chandran
    • , Shuna Colville
    •  & Robert Swingler

26. Centre for Neuroregeneration and Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK

    • Siddharthan Chandran

27. School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    • Karen E. Morrison

28. Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

    • Karen E. Morrison

29. Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK

    • Pamela J. Shaw

30. Department of Molecular Neuroscience, Institute of Neurology, University College London, UK

    • John Hardy
    •  & Alan Pittman

31. Department of Clinical Neuroscience, Institute of Neurology, University College London, UK

    • Richard W. Orrell
    •  & Katie Sidle

32. Reta Lila Weston Institute, Institute of Neurology, University College London, UK

    • Alan Pittman

33. Department of Neurodegenerative Diseases, Institute of Neurology, University College London, UK

    • Pietro Fratta

34. Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK

    • Andrea Malaspina

35. North-East London and Essex Regional Motor Neuron Disease Care Centre, London, UK

    • Andrea Malaspina

36. Department of Neurology, Medical School Hannover, Hannover, Germany

    • Susanne Petri

37. Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    • Susanna Abdulla

38. Institute for Clinical Neurobiology, University of Würzburg, Würzburg, Germany

    • Carsten Drepper
    •  & Michael Sendtner

39. Charité University Hospital, Humboldt-University, Berlin, Germany

    • Thomas Meyer

40. Department of Neurology, University of California, San Francisco, California, USA

    • Catherine Lomen-Hoerth

41. Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    • Vivianna M. Van Deerlin
    •  & John Q. Trojanowski

42. Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania Philadelphia, USA

    • Lauren Elman
    •  & Leo McCluskey

43. Neurodegeneration Research Laboratory, Bogazici University, Istanbul, Turkey

    • Nazli Basak

44. Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

    • Thomas Meitinger
    • , Peter Lichtner
    •  & Milena Blagojevic-Radivojkov

45. INSERM U930, Université François Rabelais, Tours, France

    • Christian R. Andres
    • , Cindy Maurel
    •  & Patrick Vourc'h

46. APHP, Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, UPMC Pharmacologie, Paris 6, Paris, France

    • Gilbert Bensimon
    • , Christine A. M. Payan
    •  & Peter M. Andersen

47. Department of Neurology, Ulm University, Ulm, Germany

    • Bernhard Landwehrmeyer
    • , Albert C. Ludolph
    •  & Jochen H. Weishaupt

48. INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, Paris, France

    • Alexis Brice

49. Genethon, CNRS UMR 8587, Evry, France

    • Safa Saker-Delye

50. Department of Medical Genetics, L'Institut du Cerveau et de la Moelle Épinière, Hoptial Salpêtrière, Paris

    • Alexandra Dürr

51. Department of Neurogenetics, Institute of Neurology, University College London, London, UK

    • Nicholas Wood

52. PopGen Biobank and Institute of Epidemiology, Christian Albrechts-University Kiel, Kiel, Germany

    • Lukas Tittmann
    •  & Wolfgang Lieb

53. Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany

    • Andre Franke

54. Central Institute of Mental Health; Medical Faculty Mannheim, Mannheim, Germany

    • Marcella Rietschel

55. Institute of Human Genetics, University of Bonn, Bonn, Germany

    • Sven Cichon
    • , Markus M. Nöuthen
    • , Franziska Degenhardt
    • , Stefan Herms
    • , Per Hoffmann
    •  & Andrea Hofman

56. Department of Genomics, Life and Brain Center, Bonn, Germany

    • Sven Cichon
    • , Markus M. Nöuthen
    • , Franziska Degenhardt
    • , Stefan Herms
    • , Per Hoffmann
    •  & Andrea Hofman

57. University Hospital Basel, University of Basel, Basel, Switzerland

    • Sven Cichon

58. Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland

    • Sven Cichon
    • , Stefan Herms
    •  & Per Hoffmann

59. Institute of Neuroscience and Medicine INM-1, Research Center Juelich, Juelich, Germany

    • Sven Cichon

60. Lille University, INSERM U744, Institut Pasteur de Lille, Lille, France

    • Philippe Amouyel

61. Bordeaux University, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique & CIC-1401, CHU de Bordeaux, Pole de Sante Publique, Bordeaux, France

    • Christophe Tzourio
    •  & Jean- François Dartigues

62. Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    • Andre G. Uitterlinden
    • , Fernando Rivadeneira
    •  & Karol Estrada

63. Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    • Andre G. Uitterlinden
    • , Fernando Rivadeneira
    •  & Albert Hofman

64. MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, London, UK

    • Charles Curtis

65. Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St Gallen, 9007 St Gallen, Switzerland

    • Markus Weber

66. Laboratory of Experimental Neurobiology, IRCCS 'C Mondino’ National Institute of Neurology Foundation, Pavia, Italy

    • Orietta Pansarasa
    •  & Cristina Cereda

67. Neurologic Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    • Roberto Del Bo
    •  & Giacomo P. Comi

68. Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, UPO, Università del Piemonte Orientale, Novara, Italy

    • Sandra D’Alfonso

69. Department of Neurosciences, University of Padova, Padova, Italy

    • Cinzia Bertolin
    •  & Gianni Sorarù

70. Department of Neurology, University of Eastern Piedmont, Novara, Italy

    • Letizia Mazzini

71. Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, Milano, Italy

    • Viviana Pensato
    •  & Cinzia Gellera

72. ‘Rita Levi Montalcini’ Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy

    • Andrea Calvo
    • , Cristina Moglia
    • , Maura Brunetti
    • , Federico Casale
    •  & Adriano Chio

73. Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy

    • Andrea Calvo
    • , Cristina Moglia
    • , Maura Brunetti
    •  & Adriano Chio

74. Department of Clinical research in Neurology, University of Bari ‘AMoro’, at Pia Fondazione ‘CardG Panico’, Tricase, Italy

    • Simon Arcuti
    • , Rosa Capozzo
    • , Chiara Zecca
    •  & Rosanna Tortelli

75. NEMO Clinical Center, Serena Onlus Foundation, Niguarda Ca' Granda Hostipal, Milan, Italy

    • Christian Lunetta

76. Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy

    • Silvana Penco

77. Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy

    • Nilo Riva

78. University Hospital ‘Spedali Civili’, Brescia, Italy

    • Alessandro Padovani
    •  & Massimiliano Filosto

79. Department of Neurology, Brighton and Sussex Medical School Trafford Centre for Biomedical Research, University of Sussex, Falmer, East Sussex, UK

    • P Nigel Leigh

80. Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy

    • Ettore Beghi
    •  & Elisabetta Pupillo

81. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy

    • Giancarlo Logroscino

82. Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari ‘Aldo Moro’, at Pia Fondazione Cardinale G Panico, Tricase, Lecce, Italy

    • Giancarlo Logroscino

83. Department of Neurology, University Hospital Leuven, Leuven, Belgium

    • Wim Robberecht
    •  & Philip Van Damme

84. KU Leuven-University of Leuven, Department of Neurosciences, VIB-Vesalius Research Center, Leuven, Belgium

    • Philip Van Damme

85. Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    • Robert H. Brown
    •  & John E. Landers

86. Department of Pharmacology and Clinical Neurosience, Umeå University, Umea, Sweden

    • Peter M. Andersen

87. Centre SLA, CHRU de Tours, Tours, France

    • Philippe Corcia

88. Federation des Centres SLA Tours and Limoges, LITORALS, Tours, France

    • Philippe Corcia

89. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    • R Jeroen Pasterkamp

90. Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

    • Cathryn M. Lewis
    • , Lude Franke
    •  & Juha Karjalainen

91. Department of Medical and Molecular Genetics, King’s College London, London, UK

    • Cathryn M. Lewis

92. IoPPN Genomics & Biomarker Core, Translational Genetics Group, MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, UK

    • Gerome Breen

93. NIHR Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    • Gerome Breen

94. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

    • Stephan Ripke
    • , Benjamin M. Neale
    • , Kai-How Farh
    • , Phil Lee
    • , Brendan Bulik-Sullivan
    • , Hailiang Huang
    • , Menachem Fromer
    • , Jacqueline I. Goldstein
    •  & Mark J. Daly

95. Stanley Center for Psychiatric Research, Broad Institute of MI.T. and Harvard, Cambridge, Massachusetts, USA

    • Stephan Ripke
    • , Benjamin M. Neale
    • , Phil Lee
    • , Brendan Bulik-Sullivan
    • , Richard A. Belliveau
    • , Sarah E. Bergen
    • , Elizabeth Bevilacqua
    • , Kimberley D. Chambert
    • , Menachem Fromer
    • , Giulio Genovese
    • , Colm O’Dushlaine
    • , Edward M. Scolnick
    • , Jordan W. Smoller
    • , Steven A. McCarroll
    •  & Jennifer L. Moran

96. Medical and Population Genetics Program, Broad Institute of MI.T. and Harvard, Cambridge, Massachusetts, USA

    • Benjamin M. Neale
    • , Hailiang Huang
    • , Tune H. Pers
    • , Jacqueline I. Goldstein
    • , Joel N. Hirschhorn
    • , Eli A. Stahl
    •  & Tõnu Esko

97. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

    • Benjamin M. Neale
    • , Phil Lee
    • , Menachem Fromer
    • , Jordan W. Smoller
    •  & Aarno Palotie

98. Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College, Dublin, Ireland

    • Aiden Corvin
    • , Paul Cormican
    • , Gary Donohoe
    • , Derek W. Morris
    •  & Michael Gill

99. MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK

    • James T. R. Walters
    • , Peter A Holmans
    • , Noa Carrera
    • , Nick Craddock
    • , Valentina Escott-Price
    • , Lyudmila Georgieva
    • , Marian L. Hamshere
    • , David Kavanagh
    • , Sophie E. Legge
    • , Andrew J. Pocklington
    • , Alexander L. Richards
    • , George Kirov
    • , Michael J. Owen
    •  & Michael C. O’Donovan

100. National Centre for Mental Health, Cardiff University, Cardiff, Wales

     • Peter A Holmans
     • , Nick Craddock
     • , Alexander L. Richards
     • , Michael J. Owen
     •  & Michael C. O’Donovan

101. Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, UK

     • David A. Collier
     •  & Younes Mokrab

102. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, UK

     • David A. Collier

103. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark

     • Tune H. Pers

104. Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, Massachusetts, USA

     • Tune H. Pers
     • , Joel N. Hirschhorn
     •  & Tõnu Esko

105. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

     • Ingrid Agartz
     • , Erik Söderman
     •  & Erik G. Jönsson

106. Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway

     • Ingrid Agartz

107. NORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

     • Ingrid Agartz
     • , Srdjan Djurovic
     • , Morten Mattingsdal
     • , Ingrid Melle
     •  & Ole A. Andreassen

108. Centre for Integrative Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark

     • Esben Agerbo
     •  & Preben B. Mortensen

109. National Centre for Register-based Research, Aarhus University, Aarhus, Denmark

     • Esben Agerbo
     •  & Preben B. Mortensen

110. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark

     • Esben Agerbo
     • , Ditte Demontis
     • , Thomas Hansen
     • , Manuel Mattheisen
     • , Ole Mors
     • , Line Olsen
     • , Henrik B. Rasmussen
     • , Anders D. Børglum
     • , Preben B. Mortensen
     •  & Thomas Werge

111. State Mental Hospital, Haar, Germany

     • Margot Albus

112. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA

     • Madeline Alexander
     • , Claudine Laurent
     •  & Douglas F. Levinson

113. Department of Psychiatry and Behavioral Sciences, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, USA

     • Farooq Amin

114. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA

     • Farooq Amin

115. Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA

     • Silviu A. Bacanu
     • , Tim B. Bigdeli
     • , Bradley T. Webb
     •  & Brandon K. Wormley

116. Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany

     • Martin Begemann
     • , Christian Hammer
     • , Sergi Papiol
     •  & Hannelore Ehrenreich

117. Department of Medical Genetics, University of Pécs, Pécs, Hungary

     • Judit Bene
     •  & Bela Melegh

118. Szentagothai Research Center, University of Pécs, Pécs, Hungary

     • Judit Bene
     •  & Bela Melegh

119. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

     • Sarah E. Bergen
     • , Anna K. Kähler
     • , Patrik K. E. Magnusson
     • , Christina M. Hultman
     •  & Patrick F. Sullivan

120. Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA

     • Donald W. Black

121. University Medical Center Groningen, Department of Psychiatry, University of Groningen, The Netherlands

     • Richard Bruggeman

122. School of Nursing, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA

     • Nancy G. Buccola

123. Athinoula A Martinos Center, Massachusetts General Hospital, Boston, Massachusetts, USA

     • Randy L. Buckner
     •  & Joshua L. Roffman

124. Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA

     • Randy L. Buckner

125. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA

     • Randy L. Buckner
     •  & Joshua L. Roffman

126. Department of Psychiatry, University of California at San Francisco, San Francisco, California, USA

     • William Byerley

127. Department of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Guiqing Cai
     •  & Joseph D. Buxbaum

128. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Guiqing Cai
     • , Kenneth L. Davis
     • , Elodie Drapeau
     • , Joseph I. Friedman
     • , Vahram Haroutunian
     • , Elena Parkhomenko
     • , Abraham Reichenberg
     • , Jeremy M. Silverman
     •  & Joseph D. Buxbaum

129. Centre Hospitalier du Rouvray and INSER.M. U1079 Faculty of Medicine, Rouen, France

     • Dominique Campion

130. Schizophrenia Research Institute, Sydney, Australia

     • Vaughan J. Carr
     • , Stanley V. Catts
     • , Frans A. Henskens
     • , Carmel M. Loughland
     • , Patricia T. Michie
     • , Christos Pantelis
     • , Ulrich Schall
     • , Rodney J. Scott
     •  & Assen V. Jablensky

131. School of Psychiatry, University of New South Wales, New South Wales, Sydney, Australia

     • Vaughan J. Carr

132. Royal Brisbane and Women’s Hospital, University of Queensland, Queensland, Brisbane, Australia

     • Stanley V. Catts

133. Institute of Psychology, Chinese Academy of Science, Beijing, China

     • Raymond C. K. Chan

134. Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

     • Ronald Y. L. Chan
     • , Eric Y. H. Chen
     • , Miaoxin Li
     • , Hon-Cheong So
     • , Emily H. M. Wong
     •  & Pak C. Sham

135. State Ket Laboratory for Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

     • Eric Y. H. Chen
     •  & Pak C. Sham

136. Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina, USA

     • Wei Cheng

137. Castle Peak Hospital, Hong Kong, China

     • Eric F. C. Cheung

138. Institute of Mental Health, Singapore, Singapore

     • Siow Ann Chong
     • , Jimmy Lee
     • , Kang Sim
     •  & Mythily Subramaniam

139. Department of Psychiatry, Washington University, St Louis, Missouri, USA

     • C Robert Cloninger
     •  & Dragan M. Svrakic

140. Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine and Brain and Spinal Cord Institute (ICM), Paris, France

     • David Cohen

141. Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Raritan, New Jersey, USA

     • Nadine Cohen
     • , Srihari Gopal
     • , Dai Wang
     •  & Qingqin S. Li

142. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA

     • James J. Crowley
     • , Martilias S. Farrell
     • , Paola Giusti-Rodríguez
     • , Yunjung Kim
     • , Jin P. Szatkiewicz
     • , Stephanie Williams
     •  & Patrick F. Sullivan

143. Department of Psychological Medicine, Queen Mary University of London, London, UK

     • David Curtis

144. Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK

     • David Curtis
     • , Jonathan Pimm
     • , Hugh Gurling
     •  & Andrew McQuillin

145. Sheba Medical Center, Tel Hashomer, Israel

     • Michael Davidson
     •  & Mark Weiser

146. Applied Molecular Genomics Unit, VI.B. Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium

     • Jurgen Del Favero

147. Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark

     • Ditte Demontis
     • , Manuel Mattheisen
     • , Ole Mors
     •  & Anders D. Børglum

148. Department of Biomedicine, Aarhus University, Aarhus, Denmark

     • Ditte Demontis
     • , Manuel Mattheisen
     •  & Anders D. Børglum

149. First Department of Psychiatry, University of Athens Medical School, Athens, Greece

     • Dimitris Dikeos
     •  & George N. Papadimitriou

150. Department of Psychiatry, University College Cork, Ireland

     • Timothy Dinan

151. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

     • Srdjan Djurovic

152. Cognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Ireland

     • Gary Donohoe
     •  & Derek W. Morris

153. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA

     • Jubao Duan
     • , Alan R. Sanders
     •  & Pablo V. Gejman

154. Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, Illinois, USA

     • Jubao Duan
     • , Alan R. Sanders
     •  & Pablo V. Gejman

155. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, London, UK

     • Frank Dudbridge

156. Department of Child and Adolescent Psychiatry, University Clinic of Psychiatry, Skopje, Republic of Macedonia

     • Naser Durmishi

157. Department of Psychiatry, University of Regensburg, Regensburg, Germany

     • Peter Eichhammer

158. Department of General Practice, Helsinki University Central Hospital, Helsinki, Finland

     • Johan Eriksson

159. Folkhälsan Research Center, Helsinki, Finland

     • Johan Eriksson

160. National Institute for Health and Welfare, Helsinki, Finland

     • Johan Eriksson
     •  & Veikko Salomaa

161. Translational Technologies and Bioinformatics, Pharma Research and Early Development, F. Hoffman-La Roche, Basel, Switzerland

     • Laurent Essioux

162. Department of Psychiatry, Georgetown University School of Medicine, Washington, District Of Columbia, USA

     • Ayman H. Fanous

163. Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

     • Ayman H. Fanous

164. Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA

     • Ayman H. Fanous

165. Mental Health Service Line, Washington V.A. Medical Center, Washington, District Of Columbia, USA

     • Ayman H. Fanous

166. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany

     • Josef Frank
     • , Sandra Meier
     • , Thomas G. Schulze
     • , Jana Strohmaier
     •  & Stephanie H. Witt

167. Department of Psychiatry, University of Colorado Denver, Aurora, Colorado, USA

     • Robert Freedman
     •  & Ann Olincy

168. Department of Psychiatry, University of Halle, Halle, Germany

     • Marion Friedl
     • , Ina Giegling
     • , Annette M. Hartmann
     • , Bettina Konte
     •  & Dan Rujescu

169. Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Menachem Fromer
     • , Shaun M. Purcell
     • , Panos Roussos
     • , Douglas M. Ruderfer
     • , Eli A. Stahl
     •  & Pamela Sklar

170. Department of Psychiatry, University of Munich, Munich, Germany

     • Ina Giegling
     •  & Dan Rujescu

171. Departments of Psychiatry and Human and Molecular Genetics, INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris, France

     • Stephanie Godard

172. Mental Health Research Centre, Russian Academy of Medical Sciences, Moscow, Russia

     • Vera Golimbet

173. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia

     • Jacob Gratten
     • , S Hong Lee
     • , Naomi R. Wray
     • , Peter M. Visscher
     •  & Bryan J. Mowry

174. Academic Medical Centre University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands

     • Lieuwe de Haan
     •  & Carin J. Meijer

175. Illumina, Inc., La Jolla, California, USA

     • Mark Hansen

176. Institute of Biological Psychiatry, MH.C. Sct Hans, Mental Health Services, Copenhagen, Denmark

     • Thomas Hansen
     • , Line Olsen
     • , Henrik B. Rasmussen
     •  & Thomas Werge

177. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Vahram Haroutunian
     • , Joseph D. Buxbaum
     •  & Pamela Sklar

178. JJ Peters V.A. Medical Center, Bronx, New York, USA

     • Vahram Haroutunian

179. Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, Australia

     • Frans A. Henskens

180. School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle, Australia

     • Frans A. Henskens

181. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

     • Joel N. Hirschhorn
     • , Tõnu Esko
     •  & Steven A. McCarroll

182. Section of Neonatal Screening and Hormones, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark

     • Mads V. Hollegaard
     •  & David M. Hougaard

183. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

     • Masashi Ikeda
     •  & Nakao Iwata

184. Regional Centre for Clinical Research in Psychosis, Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway

     • Inge Joa

185. Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, Spain

     • Antonio Julià
     •  & Sara Marsal

186. Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia

     • Luba Kalaydjieva

187. Perkins Institute for Medical Research, The University of Western Australia, Perth, Western Australia, Australia

     • Luba Kalaydjieva

188. Department of Medical Genetics, Medical University, Sofia, Bulgaria

     • Sena Karachanak-Yankova
     •  & Draga Toncheva

189. Department of Psychology, University of Colorado Boulder, Boulder, Colorado, USA

     • Matthew C. Keller

190. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

     • James L. Kennedy
     • , Clement C. Zai
     •  & Jo Knight

191. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

     • James L. Kennedy
     • , Clement C. Zai
     •  & Jo Knight

192. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

     • James L. Kennedy
     •  & Jo Knight

193. Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia

     • Andrey Khrunin
     • , Svetlana Limborska
     •  & Petr Slominsky

194. Latvian Biomedical Research and Study Centre, Riga, Latvia

     • Janis Klovins
     •  & Liene Nikitina-Zake

195. Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, California, USA

     • James A. Knowles
     • , Michele T. Pato
     •  & Carlos N. Pato

196. Faculty of Medicine, Vilnius University, Vilnius, Lithuania

     • Vaidutis Kucinskas
     •  & Zita Ausrele Kucinskiene

197. Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

     • Hana Kuzelova-Ptackova
     •  & Milan Macek

198. Department of Biology and Medical Genetics, Charles University Prague, Prague, Czech Republic

     • Hana Kuzelova-Ptackova
     •  & Milan Macek

199. Pierre and Marie Curie Faculty of Medicine, Paris, France

     • Claudine Laurent

200. Duke-NUS Graduate Medical School, Singapore, Singapore

     • Jimmy Lee

201. Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

     • Bernard Lerer

202. Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

     • Miaoxin Li
     •  & Pak C. Sham

203. Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chendu, Sichuan, China

     • Tao Li
     •  & Qiang Wang

204. Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

     • Kung-Yee Liang

205. Department of Psychiatry, Columbia University, New York, New York, USA

     • Jeffrey Lieberman
     •  & T Scott Stroup

206. Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, Australia

     • Carmel M. Loughland
     •  & Ulrich Schall

207. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland

     • Jan Lubinski

208. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland

     • Jouko Lönnqvist
     •  & Jaana Suvisaari

209. Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

     • Brion S. Maher

210. Department of Psychiatry, University of Bonn, Bonn, Germany

     • Wolfgang Maier

211. Centre National de la Recherche Scientifique, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Hôpital de la Pitié Salpêtrière, Paris, France

     • Jacques Mallet

212. Department of Genomics Mathematics, University of Bonn, Bonn, Germany

     • Manuel Mattheisen

213. Research Unit, Sørlandet Hospital, Kristiansand, Norway

     • Morten Mattingsdal

214. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA

     • Robert W. McCarley
     • , Raquelle I. Mesholam-Gately
     • , Larry J. Seidman
     •  & Tracey L. Petryshen

215. Virginia Boston Health Care System, Brockton, Massachusetts, USA

     • Robert W. McCarley

216. Department of Psychiatry, National University of Ireland, Galway, Ireland

     • Colm McDonald

217. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

     • Andrew M. McIntosh

218. Division of Psychiatry, University of Edinburgh, Edinburgh, UK

     • Andrew M. McIntosh
     •  & Douglas H. R. Blackwood

219. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

     • Ingrid Melle
     •  & Ole A. Andreassen

220. Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

     • Raquelle I. Mesholam-Gately
     •  & Larry J. Seidman

221. Estonian Genome Center, University of Tartu, Tartu, Estonia

     • Andres Metspalu
     • , Lili Milani
     • , Mari Nelis
     •  & Tõnu Esko

222. School of Psychology, University of Newcastle, Newcastle, Australia

     • Patricia T. Michie

223. First Psychiatric Clinic, Medical University, Sofia, Bulgaria

     • Vihra Milanova

224. Department P, Aarhus University Hospital, Risskov, Denmark

     • Ole Mors
     •  & Anders D. Børglum

225. Department of Psychiatry, Royal College of Surgeons in Ireland, Ireland

     • Kieran C. Murphy

226. King’s College London, London, UK

     • Robin M. Murray

227. Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands

     • Inez Myin-Germeys
     •  & Jim Van Os

228. Institute of Translational Medicine, University Liverpool, UK

     • Bertram Müller-Myhsok

229. Max Planck Institute of Psychiatry, Munich, Germany

     • Bertram Müller-Myhsok

230. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

     • Bertram Müller-Myhsok

231. Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany

     • Igor Nenadic

232. Department of Psychiatry, Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia

     • Deborah A. Nertney

233. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

     • Gerald Nestadt
     •  & Ann E. Pulver

234. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland

     • Kristin K. Nicodemus

235. Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA

     • Laura Nisenbaum

236. Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden

     • Annelie Nordin
     •  & Rolf Adolfsson

237. DETECT Early Intervention Service for Psychosis, Blackrock, Dublin, Ireland

     • Eadbhard O’Callaghan

238. Centre for Public Health, Institute of Clinical Sciences, Queens University Belfast, Belfast, UK

     • F Anthony O’Neill

239. Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, California, USA

     • Sang-Yun Oh

240. Institute of Psychiatry at King’s College London, London, UK

     • Jim Van Os

241. Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Melbourne, Australia

     • Christos Pantelis

242. Department of Psychiatry, University of Helsinki, Finland

     • Tiina Paunio

243. Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Helsinki, Finland

     • Tiina Paunio
     •  & Olli Pietiläinen

244. Medical Faculty, University of Belgrade, Belgrade, Serbia

     • Milica Pejovic-Milovancevic

245. Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA

     • Diana O. Perkins
     •  & Patrick F. Sullivan

246. Institute for Molecular Medicine Finland, FIMM, Helsinki, Finland

     • Olli Pietiläinen
     •  & Aarno Palotie

247. Department of Epidemiology, Harvard University, Boston, Massachusetts, USA

     • Alkes Price

248. Department of Psychiatry, University of Oxford, Oxford, UK

     • Digby Quested

249. Vir ginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA

     • Mark A. Reimers
     •  & Aaron R. Wolen

250. Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Panos Roussos
     •  & Pamela Sklar

251. PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA

     • Christian R. Schubert
     •  & Jens R. Wendland

252. Department of Psychiatry and Psychotherapy, University of Gottingen, Göttingen, Germany

     • Thomas G. Schulze

253. Psychiatry and Psychotherapy Clinic, University of Erlangen, Erlangen, Germany

     • Sibylle G. Schwab

254. Hunter New England Health Service, Newcastle, Australia

     • Rodney J. Scott

255. School of Biomedical Sciences, University of Newcastle, Newcastle, Australia

     • Rodney J. Scott

256. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA

     • Jianxin Shi

257. University of Iceland, Landspitali, National University Hospital, Reykjavik, Iceland

     • Engilbert Sigurdsson

258. Department of Psychiatry and Drug Addiction, Tbilisi State Medical University (TSMU), Tbilisi, Georgia

     • Teimuraz Silagadze

259. Research and Development, Bronx Veterans Affairs Medical Center, New York, New York, USA

     • Jeremy M. Silverman

260. Wellcome Trust Centre for Human Genetics, Oxford, UK

     • Chris C. A. Spencer

261. deCODE Genetics, Reykjavik, Iceland

     • Hreinn Stefansson
     • , Stacy Steinberg
     •  & Kari Stefansson

262. Department of Clinical Neurology, Medical University of Vienna, Vienna, Austria

     • Elisabeth Stogmann
     •  & Fritz Zimprich

263. Lieber Institute for Brain Development, Baltimore, Maryland, USA

     • Richard E. Straub
     •  & Daniel R. Weinberger

264. Department of Medical Genetics, University Medical Centre, Utrecht, The Netherlands

     • Eric Strengman

265. Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands

     • Eric Strengman

266. Berkshire Healthcare NH.S. Foundation Trust, Bracknell, UK

     • Srinivas Thirumalai

267. Section of Psychiatry, University of Verona, Verona, Italy

     • Sarah Tosato

268. Department of Psychiatry, University of Oulu, Oulu, Finland

     • Juha Veijola

269. University Hospital of Oulu, Oulu, Finland

     • Juha Veijola

270. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland

     • John Waddington

271. Health Research Board, Dublin, Ireland

     • Dermot Walsh

272. Department of Psychiatry and Clinical Neurosciences, School of Psychiatry and Clinical Neurosciences, Queen Elizabeth I.I. Medical Centre, Perth, Western Australia, Australia

     • Dieter B. Wildenauer

273. Department of Psychological Medicine and Neurology, MR.C. Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, Wales, UK

     • Nigel M. Williams

274. Computational Sciences CoE, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA

     • Hualin Simon Xi

275. Human Genetics, Genome Institute of Singapore, Singapore, Singapore

     • Xuebin Zheng
     •  & Jianjun Liu

276. University College London, London, UK

     • Elvira Bramon

277. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA

     • Joseph D. Buxbaum

278. Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel

     • Ariel Darvasi

279. Neuroscience Discovery and Translational Area, Pharma Research and Early Development, F. Hoffman-La Roche, Basel, Switzerland

     • Enrico Domenici

280. School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, Australia

     • Assen V. Jablensky

281. The Perkins Institute of Medical Research, Perth, Australia

     • Assen V. Jablensky

282. UWA Centre for Clinical Research in Neuropsychiatry

     • Assen V. Jablensky

283. Virginia Institute for Psychiatric and Behavioral Genetics, Departments of Psychiatry and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA

     • Kenneth S. Kendler
     •  & Brien P. Riley

284. The Feinstein Institute for Medical Research, Manhasset, New York, USA

     • Todd Lencz
     •  & Anil K. Malhotra

285. The Hofstra NS-LIJ School of Medicine, Hempstead, New York, USA

     • Todd Lencz
     •  & Anil K. Malhotra

286. The Zucker Hillside Hospital, Glen Oaks, New York, USA

     • Todd Lencz
     •  & Anil K. Malhotra

287. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

     • Jianjun Liu

288. Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia

     • Bryan J. Mowry

289. The Broad Institute of MI.T. and Harvard, Cambridge, Massachusetts, USA

     • Aarno Palotie
     •  & Tracey L. Petryshen

290. Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA

     • Tracey L. Petryshen

291. Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands

     • Danielle Posthuma

292. Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, V.U. University Medical Center Amsterdam, Amsterdam, The Netherlands

     • Danielle Posthuma

293. Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands

     • Danielle Posthuma

294. University of Aberdeen, Institute of Medical Sciences, Aberdeen, Scotland, UK

     • David St Clair

295. Departments of Psychiatry, Neurology, Neuroscience and Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

     • Daniel R. Weinberger

296. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

     • Thomas Werge

Consortia

1. Project MinE GWAS Consortium

   • Aleksey Shatunov
   • , Annelot M. Dekker
   • , Frank P. Diekstra
   • , Sara L. Pulit
   • , Rick A. A. van der Spek
   • , Perry T. C. van Doormaal
   • , William Sproviero
   • , Ashley R. Jones
   • , Garth A. Nicholson
   • , Dominic B. Rowe
   • , Roger Pamphlett
   • , Matthew C. Kiernan
   • , Denis Bauer
   • , Tim Kahlke
   • , Kelly Williams
   • , Filip Eftimov
   • , Isabella Fogh
   • , Nicola Ticozzi
   • , Kuang Lin
   • , Stéphanie Millecamps
   • , François Salachas
   • , Vincent Meininger
   • , Mamede de Carvalho
   • , Susana Pinto
   • , Jesus S. Mora
   • , Ricardo Rojas-García
   • , Meraida Polak
   • , Siddharthan Chandran
   • , Shuna Colville
   • , Robert Swingler
   • , Karen E. Morrison
   • , Pamela J. Shaw
   • , John Hardy
   • , Richard W. Orrell
   • , Alan Pittman
   • , Katie Sidle
   • , Pietro Fratta
   • , Andrea Malaspina
   • , Susanne Petri
   • , Susanna Abdulla
   • , Carsten Drepper
   • , Michael Sendtner
   • , Thomas Meyer
   • , Martina Wiedau-Pazos
   • , Catherine Lomen-Hoerth
   • , Vivianna M. Van Deerlin
   • , John Q. Trojanowski
   • , Lauren Elman
   • , Leo McCluskey
   • , Nazli Basak
   • , Thomas Meitinger
   • , Peter Lichtner
   • , Milena Blagojevic-Radivojkov
   • , Christian R. Andres
   • , Cindy Maurel
   • , Gilbert Bensimon
   • , Bernhard Landwehrmeyer
   • , Alexis Brice
   • , Christine A. M. Payan
   • , Safa Saker-Delye
   • , Alexandra Dürr
   • , Nicholas Wood
   • , Lukas Tittmann
   • , Wolfgang Lieb
   • , Andre Franke
   • , Marcella Rietschel
   • , Sven Cichon
   • , Markus M. Nöuthen
   • , Philippe Amouyel
   • , Christophe Tzourio
   • , Jean- François Dartigues
   • , Andre G. Uitterlinden
   • , Fernando Rivadeneira
   • , Karol Estrada
   • , Albert Hofman
   • , Charles Curtis
   • , Anneke J. van der Kooi
   • , Marianne de Visser
   • , Markus Weber
   • , Christopher E. Shaw
   • , Bradley N. Smith
   • , Orietta Pansarasa
   • , Cristina Cereda
   • , Roberto Del Bo
   • , Giacomo P. Comi
   • , Sandra D’Alfonso
   • , Cinzia Bertolin
   • , Gianni Sorarù
   • , Letizia Mazzini
   • , Viviana Pensato
   • , Cinzia Gellera
   • , Cinzia Tiloca
   • , Antonia Ratti
   • , Andrea Calvo
   • , Cristina Moglia
   • , Maura Brunetti
   • , Simon Arcuti
   • , Rosa Capozzo
   • , Chiara Zecca
   • , Christian Lunetta
   • , Silvana Penco
   • , Nilo Riva
   • , Alessandro Padovani
   • , Massimiliano Filosto
   • , Ian Blair
   • , P Nigel Leigh
   • , Federico Casale
   • , Adriano Chio
   • , Ettore Beghi
   • , Elisabetta Pupillo
   • , Rosanna Tortelli
   • , Giancarlo Logroscino
   • , John Powell
   • , Albert C. Ludolph
   • , Jochen H. Weishaupt
   • , Wim Robberecht
   • , Philip Van Damme
   • , Robert H. Brown
   • , Jonathan Glass
   • , John E. Landers
   • , Peter M. Andersen
   • , Philippe Corcia
   • , Patrick Vourc'h
   • , Vincenzo Silani
   • , Michael A. van Es
   • , R Jeroen Pasterkamp
   • , Cathryn M. Lewis
   •  & Gerome Breen

2. Schizophrenia Working Group of the Psychiatric Genomics Consortium

   • Stephan Ripke
   • , Benjamin M. Neale
   • , Aiden Corvin
   • , James T. R. Walters
   • , Kai-How Farh
   • , Peter A Holmans
   • , Phil Lee
   • , Brendan Bulik-Sullivan
   • , David A. Collier
   • , Hailiang Huang
   • , Tune H. Pers
   • , Ingrid Agartz
   • , Esben Agerbo
   • , Margot Albus
   • , Madeline Alexander
   • , Farooq Amin
   • , Silviu A. Bacanu
   • , Martin Begemann
   • , Richard A. Belliveau
   • , Judit Bene
   • , Sarah E. Bergen
   • , Elizabeth Bevilacqua
   • , Tim B. Bigdeli
   • , Donald W. Black
   • , Richard Bruggeman
   • , Nancy G. Buccola
   • , Randy L. Buckner
   • , William Byerley
   • , Wiepke Cahn
   • , Guiqing Cai
   • , Dominique Campion
   • , Rita M. Cantor
   • , Vaughan J. Carr
   • , Noa Carrera
   • , Stanley V. Catts
   • , Kimberley D. Chambert
   • , Raymond C. K. Chan
   • , Ronald Y. L. Chan
   • , Eric Y. H. Chen
   • , Wei Cheng
   • , Eric F. C. Cheung
   • , Siow Ann Chong
   • , C Robert Cloninger
   • , David Cohen
   • , Nadine Cohen
   • , Paul Cormican
   • , Nick Craddock
   • , James J. Crowley
   • , David Curtis
   • , Michael Davidson
   • , Kenneth L. Davis
   • , Franziska Degenhardt
   • , Jurgen Del Favero
   • , Ditte Demontis
   • , Dimitris Dikeos
   • , Timothy Dinan
   • , Srdjan Djurovic
   • , Gary Donohoe
   • , Elodie Drapeau
   • , Jubao Duan
   • , Frank Dudbridge
   • , Naser Durmishi
   • , Peter Eichhammer
   • , Johan Eriksson
   • , Valentina Escott-Price
   • , Laurent Essioux
   • , Ayman H. Fanous
   • , Martilias S. Farrell
   • , Josef Frank
   • , Lude Franke
   • , Robert Freedman
   • , Nelson B. Freimer
   • , Marion Friedl
   • , Joseph I. Friedman
   • , Menachem Fromer
   • , Giulio Genovese
   • , Lyudmila Georgieva
   • , Ina Giegling
   • , Paola Giusti-Rodríguez
   • , Stephanie Godard
   • , Jacqueline I. Goldstein
   • , Vera Golimbet
   • , Srihari Gopal
   • , Jacob Gratten
   • , Lieuwe de Haan
   • , Christian Hammer
   • , Marian L. Hamshere
   • , Mark Hansen
   • , Thomas Hansen
   • , Vahram Haroutunian
   • , Annette M. Hartmann
   • , Frans A. Henskens
   • , Stefan Herms
   • , Joel N. Hirschhorn
   • , Per Hoffmann
   • , Andrea Hofman
   • , Mads V. Hollegaard
   • , David M. Hougaard
   • , Masashi Ikeda
   • , Inge Joa
   • , Antonio Julià
   • , Luba Kalaydjieva
   • , Sena Karachanak-Yankova
   • , Juha Karjalainen
   • , David Kavanagh
   • , Matthew C. Keller
   • , James L. Kennedy
   • , Andrey Khrunin
   • , Yunjung Kim
   • , Janis Klovins
   • , James A. Knowles
   • , Bettina Konte
   • , Vaidutis Kucinskas
   • , Zita Ausrele Kucinskiene
   • , Hana Kuzelova-Ptackova
   • , Anna K. Kähler
   • , Claudine Laurent
   • , Jimmy Lee
   • , S Hong Lee
   • , Sophie E. Legge
   • , Bernard Lerer
   • , Miaoxin Li
   • , Tao Li
   • , Kung-Yee Liang
   • , Jeffrey Lieberman
   • , Svetlana Limborska
   • , Carmel M. Loughland
   • , Jan Lubinski
   • , Jouko Lönnqvist
   • , Milan Macek
   • , Patrik K. E. Magnusson
   • , Brion S. Maher
   • , Wolfgang Maier
   • , Jacques Mallet
   • , Sara Marsal
   • , Manuel Mattheisen
   • , Morten Mattingsdal
   • , Robert W. McCarley
   • , Colm McDonald
   • , Andrew M. McIntosh
   • , Sandra Meier
   • , Carin J. Meijer
   • , Bela Melegh
   • , Ingrid Melle
   • , Raquelle I. Mesholam-Gately
   • , Andres Metspalu
   • , Patricia T. Michie
   • , Lili Milani
   • , Vihra Milanova
   • , Younes Mokrab
   • , Derek W. Morris
   • , Ole Mors
   • , Kieran C. Murphy
   • , Robin M. Murray
   • , Inez Myin-Germeys
   • , Bertram Müller-Myhsok
   • , Mari Nelis
   • , Igor Nenadic
   • , Deborah A. Nertney
   • , Gerald Nestadt
   • , Kristin K. Nicodemus
   • , Liene Nikitina-Zake
   • , Laura Nisenbaum
   • , Annelie Nordin
   • , Eadbhard O’Callaghan
   • , Colm O’Dushlaine
   • , F Anthony O’Neill
   • , Sang-Yun Oh
   • , Ann Olincy
   • , Line Olsen
   • , Jim Van Os
   • , Christos Pantelis
   • , George N. Papadimitriou
   • , Sergi Papiol
   • , Elena Parkhomenko
   • , Michele T. Pato
   • , Tiina Paunio
   • , Milica Pejovic-Milovancevic
   • , Diana O. Perkins
   • , Olli Pietiläinen
   • , Jonathan Pimm
   • , Andrew J. Pocklington
   • , Alkes Price
   • , Ann E. Pulver
   • , Shaun M. Purcell
   • , Digby Quested
   • , Henrik B. Rasmussen
   • , Abraham Reichenberg
   • , Mark A. Reimers
   • , Alexander L. Richards
   • , Joshua L. Roffman
   • , Panos Roussos
   • , Douglas M. Ruderfer
   • , Veikko Salomaa
   • , Alan R. Sanders
   • , Ulrich Schall
   • , Christian R. Schubert
   • , Thomas G. Schulze
   • , Sibylle G. Schwab
   • , Edward M. Scolnick
   • , Rodney J. Scott
   • , Larry J. Seidman
   • , Jianxin Shi
   • , Engilbert Sigurdsson
   • , Teimuraz Silagadze
   • , Jeremy M. Silverman
   • , Kang Sim
   • , Petr Slominsky
   • , Jordan W. Smoller
   • , Hon-Cheong So
   • , Chris C. A. Spencer
   • , Eli A. Stahl
   • , Hreinn Stefansson
   • , Stacy Steinberg
   • , Elisabeth Stogmann
   • , Richard E. Straub
   • , Eric Strengman
   • , Jana Strohmaier
   • , T Scott Stroup
   • , Mythily Subramaniam
   • , Jaana Suvisaari
   • , Dragan M. Svrakic
   • , Jin P. Szatkiewicz
   • , Erik Söderman
   • , Srinivas Thirumalai
   • , Draga Toncheva
   • , Sarah Tosato
   • , Juha Veijola
   • , John Waddington
   • , Dermot Walsh
   • , Dai Wang
   • , Qiang Wang
   • , Bradley T. Webb
   • , Mark Weiser
   • , Dieter B. Wildenauer
   • , Nigel M. Williams
   • , Stephanie Williams
   • , Stephanie H. Witt
   • , Aaron R. Wolen
   • , Emily H. M. Wong
   • , Brandon K. Wormley
   • , Hualin Simon Xi
   • , Clement C. Zai
   • , Xuebin Zheng
   • , Fritz Zimprich
   • , Naomi R. Wray
   • , Kari Stefansson
   • , Peter M. Visscher
   • , Rolf Adolfsson
   • , Ole A. Andreassen
   • , Douglas H. R. Blackwood
   • , Elvira Bramon
   • , Joseph D. Buxbaum
   • , Anders D. Børglum
   • , Ariel Darvasi
   • , Enrico Domenici
   • , Hannelore Ehrenreich
   • , Tõnu Esko
   • , Pablo V. Gejman
   • , Michael Gill
   • , Hugh Gurling
   • , Christina M. Hultman
   • , Nakao Iwata
   • , Assen V. Jablensky
   • , Erik G. Jönsson
   • , Kenneth S. Kendler
   • , George Kirov
   • , Jo Knight
   • , Todd Lencz
   • , Douglas F. Levinson
   • , Qingqin S. Li
   • , Jianjun Liu
   • , Anil K. Malhotra
   • , Steven A. McCarroll
   • , Andrew McQuillin
   • , Jennifer L. Moran
   • , Preben B. Mortensen
   • , Bryan J. Mowry
   • , Michael J. Owen
   • , Aarno Palotie
   • , Carlos N. Pato
   • , Tracey L. Petryshen
   • , Danielle Posthuma
   • , Brien P. Riley
   • , Dan Rujescu
   • , Pak C. Sham
   • , Pamela Sklar
   • , David St Clair
   • , Daniel R. Weinberger
   • , Jens R. Wendland
   • , Thomas Werge
   • , Mark J. Daly
   • , Patrick F. Sullivan
   •  & Michael C. O’Donovan

Contributions

O.H., J.H.V. and A.A.-C. conceived the study. R.L.McL., D.S., W.v.R., K.R.v.E., M.O’B., D.G.B., A.A.-C., L.H.v.d.B., J.J.L., O.H. and J.H.V. contributed to study design. R.L.McL., D.S. and W.v.R. conducted the analyses. R.L.McL., D.S., O.H., J.J.L. and J.H.V. drafted the manuscript. R.S.K., R.A.O. and A.G. provided data and critical revision of the manuscript. The Project MinE GWAS Consortium and Schizophrenia Working Group of the Psychiatric Genomics Consortium provided data. R.L.Mc.L. and D.S. contributed equally. J.J.L., O.H. and J.H.V. jointly directed the work.

Competing interests

O.H. has received speaking honoraria from Novartis, Biogen Idec, Sanofi Aventis and Merck-Serono. She has been a member of advisory panels for Biogen Idec, Allergen, Ono Pharmaceuticals, Novartis, Cytokinetics and Sanofi Aventis. She serves as Editor-in-Chief of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. L.H.v.d.B. serves on scientific advisory boards for Prinses Beatrix Spierfonds, Thierry Latran Foundation, Baxalta, Cytokinetics and Biogen, serves on the Editorial Board of the Journal of Neurology, Neurosurgery, and Psychiatry, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, and Journal of Neuromuscular Diseases. A.A.C. has served on advisory panels for Biogen Idec, Cytokinetics, GSK, OrionPharma and Mitsubishi-Tanabe, serves on the Editorial Boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and F1000, and receives royalties for The Brain: A Beginner’s Guide, OneWorld Publications, and Genetics of Complex Human Diseases, Cold Spring Harbor Laboratory Press. The remaining authors declare no competing financial interests.

Corresponding author

Correspondence to Russell L. McLaughlin.

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