Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy.
Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy.
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人格和认知特征的多变量遗传分析揭示了丰富的多效性。
DOI：
10.1038/s41562-023-01630-9
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发表时间：
2023
影响因子：
29.9
通讯作者：
Hindley G
中科院分区：
文献类型：
--
作者：
Hindley G
个性和认知功能是可遗传的心理特征，其遗传基础可能分布在相互关联的大脑功能上。以前的研究通常将这些复杂的心理特征视为不同的概念。我们将多变量综合统计检验应用于来自英国生物库的35项神经质和认知功能指标的全基因组关联研究(n= 336,993)。我们确定了431个显著相关的遗传基因座，证据表明，在人格和认知功能领域中，存在丰富的共同遗传关联。功能特征表明，在所有测试的脑组织和脑特定基因组中，具有显著组织特异性表达的基因。我们根据我们的多变量发现，对五大人格特征和认知功能进行了独立的全基因组关联研究，促进了其他人格特征的基因发现，并改善了多基因预测。这些发现促进了我们对这些复杂心理特征的多基因结构的理解，表明多基因遗传效应在人格和认知功能等更高级别的心理功能领域中的显着性。
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.