Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a 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 identified loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results captures variation in a broad range of behavioral and medical outcomes that were not part of our 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 condition.

中文翻译：

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对150万人的多元基因组分析可识别与成瘾，反社会行为和健康相关的基因

与自我调节有关的行为和障碍，例如物质使用，反社会行为和多动症，统称为外在化，具有共同的遗传责任。我们应用了一种多变量方法，该方法利用了外在性状之间的遗传相关性进行全基因组关联分析。通过汇总约150万人的数据，我们的方法在统计上比单性状分析更强大，并且可以识别500多个遗传基因座。鉴定出的基因座富含脑中表达的基因，并与神经系统发育有关。根据我们的结果构建的多基因评分可捕获各种行为和医学结果的差异，这不是我们全基因组分析的一部分，包括迄今为止尚缺乏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。我们的发现与这样的观点是一致的，即自我调节方面的持续困难可以被概念化为神经发育状况。