Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
MRC Centre for Drug Safety Science, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Sci Adv. 2020 Jan 15;6(3):eaay5034. doi: 10.1126/sciadv.aay5034. eCollection 2020 Jan.
High alcohol consumption is a risk factor for morbidity and mortality, yet few genetic loci have been robustly associated with alcohol intake. Here, we use U.K. Biobank ( = 125,249) and GERA ( = 47,967) datasets to determine genetic factors associated with extreme population-level alcohol consumption and examine the functional validity of outcomes using model organisms and in silico techniques. We identified six loci attaining genome-wide significant association with alcohol consumption after meta-analysis and meeting our criteria for replication: (lead SNP: rs1229984), (rs13130794), (rs144198753), (rs1260326), (rs13107325), and (rs11214609). A conserved role in phenotypic responses to alcohol was observed for all genetic targets available for investigation (, and ) in . Evidence of causal links to lung cancer, and shared genetic architecture with gout and hypertension was also found. These findings offer insight into genes, pathways, and relationships for disease risk associated with high alcohol consumption.
大量饮酒是发病和死亡的一个风险因素，但很少有遗传位点与饮酒量有明显关联。在这里，我们使用英国生物银行（n=125249）和 GERA 数据集（n=47967）来确定与人群中极端饮酒量相关的遗传因素，并使用模式生物和计算技术来检查结果的功能有效性。我们通过荟萃分析确定了六个与饮酒量达到全基因组显著关联并符合我们复制标准的位点：（lead SNP：rs1229984），（rs13130794），（rs144198753），（rs1260326），（rs13107325）和（rs11214609）。在模式生物 中，所有可用于研究的遗传靶点（、和）在对酒精的表型反应中表现出保守作用。还发现与肺癌之间存在因果关系的证据，以及与痛风和高血压的遗传结构共享。这些发现为与大量饮酒相关的疾病风险的基因、途径和关系提供了深入了解。
