Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
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DOI：
10.1038/s41467-019-09480-8
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发表时间：
2019-04-02
影响因子：
16.6
通讯作者：
Gelernter, Joel
中科院分区：
文献类型：
--
作者：
Kranzler, Henry R.;Zhou, Hang;Gelernter, Joel
酒精消费水平和酒精使用障碍（AUD）诊断是中度遗传性状。我们使用纵向酒精使用障碍识别测试-消费（AUDIT-C）评分和多血统百万退伍军人计划样本（N = 274，424）中的AUD诊断对这些特征进行全基因组关联研究。我们确定了18个全基因组显著位点：5个与两个性状相关，8个仅与AUDIT-C相关，5个仅与AUD诊断相关。在两个独立样本中，这两个特征的多基因风险评分（PRS）与酒精相关疾病相关。虽然一个显着的遗传相关性反映了性状之间的重叠，188个非酒精相关性状的遗传相关性显着不同的两个性状，因为与性状的PRS相关的表型。细胞类型组划分遗传力富集分析也区分这两个性状。我们的结论是，虽然大量饮酒是AUD的一个关键风险因素，但它不是该疾病的充分原因。
Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits' PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.