多效性
遗传建筑学
五大性格特征
人格
全基因组关联研究
认知
神经质
心理学
生物
多元统计
影像遗传学
遗传学
数量性状位点
表型
基因
神经影像学
单核苷酸多态性
精神科
社会心理学
机器学习
基因型
计算机科学
作者
Guy Hindley,Alexey Shadrin,Dennis van der Meer,Nadine Parker,Weiqiu Cheng,Kevin O’Connell,Shahram Bahrami,Aihua Lin,Nils Eiel Steen,Børge Holen,Thomas Bjella,Ian J. Deary,Gail Davies,W. David Hill,Jan Bressler,Sudha Seshadri,Chun Chieh Fan,Torill Ueland,Srdjan Djurovic,Olav B. Smeland,Oleksandr Frei,Anders M. Dale,Ole A. Andreassen
标识
DOI:10.1038/s41562-023-01630-9
摘要
Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the ‘pleiotropy-informed’ multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function. Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.
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