Shared genetic factors contribute to the high degree of comorbidity among externalizing problems (e.g. substance use and antisocial behavior). We leverage this common genetic etiology to identify genetic influences externalizing problems in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7568; African ancestry = 3274). We performed a family-based genome-wide association study (GWAS) on externalizing scores derived from criterion counts of five DSM disorders (alcohol dependence, alcohol abuse, illicit drug dependence, illicit drug abuse, and either antisocial personality disorder or conduct disorder). We meta analyzed these results with a similar measure of externalizing in an independent sample, Spit for Science (combined sample N = 15,112). We did not discover any robust genome-wide significant signals. Polygenic scores derived from the ancestry-specific GWAS summary statistics predicted externalizing problems in an independent European ancestry sample, but not in those of African ancestry. However, these PRS were no longer significant after adjusting for multiple testing. Larger samples with deep phenotyping are necessary for the discovery of SNPs related to externalizing problems.

中文翻译：

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基于家庭的全基因组外部化行为研究。

共有的遗传因素导致了外部化问题（例如物质使用和反社会行为）中的高度合并症。我们利用这种常见的遗传病因从酒精中毒遗传学合作研究（欧洲血统= 7568；非洲血统= 3274）中识别参与者的遗传影响外在问题。我们进行了一项基于家庭的全基因组关联研究（GWAS），该研究从五种DSM障碍（酒精依赖，酒精滥用，非法药物依赖，非法药物滥用以及反社会人格障碍或品行障碍）的标准计数得出的外部化得分。我们使用独立样本Spit for Science（合并样本N = 15,112）中类似的外部化措施对这些结果进行了荟萃分析。我们没有发现任何健壮的全基因组重要信号。从特定于祖先的GWAS汇总统计数据得出的多基因评分可预测独立欧洲祖先样本中的外部化问题，而非洲祖先则没有。但是，经过多次测试调整后，这些PRS不再重要。具有深表型的较大样本对于发现与外部化问题相关的SNP必不可少。