Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates.

与自我调节相关的行为和障碍，如物质使用、反社会行为和注意力缺陷/多动障碍，统称为外化，并具有共同的遗传责任。我们应用了一种多变量方法，利用外化性状之间的遗传相关性进行全基因组关联分析。通过汇集来自约 150 万人的数据，我们的方法在统计上比单一性状分析更强大，并识别了 500 多个基因位点。这些位点丰富了大脑中表达的与神经系统发育相关的基因。根据我们的结果构建的多基因评分预测了一系列行为和医学结果，这些结果不属于全基因组分析的一部分，包括迄今为止缺乏表现良好的多基因评分的特征，例如阿片类药物使用障碍，自杀、艾滋病毒感染、刑事定罪和失业。我们的研究结果与以下观点一致，即持续存在的自我调节困难可以被概念化为一种神经发育特征，具有复杂而深远的社会和健康相关性。