Abstract
Major mental disorders are highly prevalent and make a substantial contribution to the global disease burden. It is known that mental disorders share clinical characteristics, and genome-wide association studies (GWASs) have recently provided evidence for shared genetic factors as well. Genetic overlaps are usually identified at the single-marker level. Here, we aimed to identify genetic overlaps at the gene level between 7 mental disorders (schizophrenia, autism spectrum disorder, major depressive disorder, anorexia nervosa, ADHD, bipolar disorder and anxiety), 8 brain morphometric traits, 2 cognitive traits (educational attainment and general cognitive function) and 9 personality traits (subjective well-being, depressive symptoms, neuroticism, extraversion, openness to experience, agreeableness and conscientiousness, children’s aggressive behaviour, loneliness) based on publicly available GWASs. We performed systematic conditional regression analyses to identify independent signals and select loci associated with more than one trait. We identified 48 genes containing independent markers associated with several traits (pleiotropy at the gene level). We also report 9 genes with different markers that show independent associations with single traits (allelic heterogeneity). This study demonstrates that mental disorders and related traits do show pleiotropy at the gene level as well as the single-marker level. The identification of these genes might be important for prioritizing further deep genotyping, functional studies, or drug targeting.
Highlights
Many mental disorders share features such as clinical symptoms, cognitive deficits or drug prescriptions
We selected 7 GWASs for mental disorders, together with 20 GWASs for cognitive, personality and brain morphology traits that have been suggested as potential endophenotypes for those mental disorders [30, 33, 34, 40, 63, 64], or have some genetic overlap with those mental disorders
Using the summary statistics from all 27 GWASs, we identified a total of 2190 unique associated SNPs after conditional regression [25]
Summary
Many mental disorders share features such as clinical symptoms, cognitive deficits or drug prescriptions. Genetic overlaps have been reported within the domain of mental disorders [9, 12] or between psychiatric and cognitive traits [13,14,15]. In these studies, the underlying assumption is that the genetic correlation between traits arises due to the presence of markers affecting both traits, i.e. pleiotropy at the SNP level
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