Jorgenson E, Thai K K, Hoffmann T J, Sakoda L C, Kvale M N, Banda Y, Schaefer C, Risch N, Mertens J, Weisner C, Choquet H
Kaiser Permanente Division of Research, Oakland, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
Mol Psychiatry. 2017 Sep;22(9):1359-1367. doi: 10.1038/mp.2017.101. Epub 2017 May 9.
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects' alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10 for drinker status and beta=-0.19, P=1.91 × 10 for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10 and beta=-0.21, P=2.58 × 10, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10 for drinks/week and OR=0.96, P=4.08 × 10 for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10 for drinks/week and OR=1.04, P=5 × 10 for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.
饮酒是一种由遗传和环境因素共同决定的复杂性状，与酒精使用障碍的风险相关。尽管已有少数基因位点被报道与饮酒量的变异有关，但据估计遗传因素只能解释饮酒量变异的大约一半，这表明还有其他位点有待发现。我们在大型成人健康与衰老遗传流行病学研究（GERA）队列中，对四个种族/族裔群体（非西班牙裔白人、西班牙裔/拉丁裔、东亚人和非裔美国人）的饮酒情况进行了全基因组关联研究（GWAS）。我们基于自我报告信息，考察了反映受试者过去一年饮酒情况的两种统计学上独立的表型：是否饮酒（饮酒者/非饮酒者状态）以及饮酒者每周的饮酒量（每周饮酒量）。我们在每个种族/族裔群体中评估了这两种饮酒表型，并在一项包含总共86627名个体的跨种族荟萃分析中进行了评估。我们观察到，在东亚人中，先前报道的ALDH2基因中的单核苷酸多态性（SNP）rs671与饮酒者状态之间存在最强关联（优势比（OR）=0.40，P=2.28×10），并且在同一群体中对每周饮酒量也有影响（β=-0.17，P=5.42×10）。我们还在非西班牙裔白人中观察到，先前报道的ADH1B基因中的SNP rs1229984与两种饮酒表型均存在全基因组显著关联（饮酒者状态的OR=0.79，P=2.47×10；每周饮酒量的β=-0.19，P=1.91×10），这在西班牙裔/拉丁裔中得到了重复（分别为OR=0.72，P=4.35×10和β=-0.21，P=2.58×10）。尽管先前的研究报道了ADH1B和ALDH2对终生指标（如酒精依赖风险）的影响，但我们的研究进一步证明了这些相同基因对平均饮酒横断面指标的影响。我们的跨种族荟萃分析证实了最近的研究结果，即KLB和GCKR基因座与饮酒有关，观察到rs7686419与每周饮酒量之间的关联最强（β=-0.04，P=3.41×10；饮酒者状态的OR=0.96，P=4.08×10），以及rs4665985与每周饮酒量之间的关联最强（β=0.04，P=2.26×10；饮酒者状态的OR=1.04，P=5×10）。最后，我们还获得了证实性结果，扩展了先前关于非西班牙裔白人中AUTS2、SGOL1和SERPINC1基因与饮酒性状相关的研究发现。
