Kavli Affiliate: Anders Dale
| Authors: Guy Hindley, Alexey A Shadrin, Dennis van der Meer, Nadine Parker, Weiqiu Cheng, Kevin S O’Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Borge Holen, Thomas Bjella, Chun Chieh Fan, Torill Uelan, Srdjan Djurovic, Olav B Smeland, Oleksandr Frei, Anders Dale and Ole Andreassen
| Summary:
Personality and cognition are heritable mental traits, and their genetic determinants may be distributed across interconnected brain functions. However, previous studies have employed univariate approaches which reduce complex traits to summary measures. We applied the “pleiotropy-informed” multivariate omnibus statistical test (MOSTest) to genome-wide association studies (GWAS) of 35 item and task-level measures of neuroticism and cognition from the UK Biobank (n=336,993). We identified 431 significant genetic loci and found evidence of abundant pleiotropy across personality and cognitive domains. Functional characterisation implicated genes with significant tissue-specific expression in all tested brain tissues and enriched in brain-specific gene-sets. We conditioned independent GWAS of the Big 5 personality traits and cognition on our multivariate findings, which boosted genetic discovery in other personality traits and improved polygenic prediction. These findings advance our understanding of the polygenic architecture of complex mental traits, indicating a prominence of pleiotropic genetic effects across higher-order domains of mental function.