Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study.
Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study.
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在大型多种族基因组的关联研究中，饮酒差异的遗传因素因种族/种族而异。
DOI：
10.1038/mp.2017.101
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发表时间：
2017-09
影响因子：
11
通讯作者：
Choquet H
中科院分区：
文献类型：
--
作者：
Jorgenson E;Thai KK;Hoffmann TJ;Sakoda LC;Kvale MN;Banda Y;Schaefer C;Risch N;Mertens J;Weisner C;Choquet H
饮酒是一个由遗传和环境因素决定的复杂特征，与酒精使用障碍的风险相关。虽然有少数基因座被报道与饮酒的差异有关，但据估计，遗传因素可以解释饮酒差异的大约一半，这表明还有更多的基因座有待发现。我们在成人健康和老龄化中的大型遗传流行病学研究(GERA)队列中对酒精消费进行了全基因组关联研究，研究对象为四个种族/民族：非西班牙裔白人、西班牙裔/拉丁裔、东亚人和非裔美国人。我们基于自我报告的信息，检查了两种统计上独立的表型，它们反映了受试者在过去一年中的饮酒情况：是否饮酒(饮酒者/非饮酒者状态)，以及饮酒者每周正常饮酒量(饮酒量/周)。我们在每个种族/民族组中评估了这两种饮酒表型，并在一项包括总共86627人的跨种族联合荟萃分析中进行了评估。我们观察到先前报道的ALDH2型单核苷酸多态rs671与东亚人饮酒状态(OR=0.40，p=2.28×10−72)以及同一组人每周饮酒量(β=−0.17，p=5.42×10−4)之间的最强关联。我们还观察到在非西班牙裔白人中，先前报道的ADH1B基因rs1229984与两种饮酒表型(饮酒状态的OR=0.79，p=2.47×10−20和饮酒状态的β=−0.19，p=1.91×10−35)之间存在显著的全基因组显著关联，这两种表型在拉美裔/拉丁裔中都是如此(分别为OR=0.72，p=4.35×10−7和β=−0.21，p=2.58×10−6)。虽然先前的研究报告了ADH1B和ALDH2对酒精依赖风险等终生指标的影响，但我们的研究进一步证明了相同基因对平均饮酒量的横截面指标的影响。我们的跨种族Meta分析证实了最近发现的与饮酒有关的KLB和GCKR基因座，其中rs7686419(β=−0.04，p=3.41×10−10/周饮酒，OR=0.96p=4.08×10−5表示饮酒状态)和rs4665985(β=0.04，p=2.26×10−8，OR=1.04，p=5.00×10−4表示饮酒状态)与饮酒密切相关。最后，我们还获得了确凿的结果，扩展了先前的发现，即AUTS2、SGOL1和SERPINC1基因与非西班牙裔白人的饮酒特征有关。
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. While 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 (OR=0.40, p=2.28×10−72) in East Asians, and also an effect on drinks/week (beta=−0.17, p=5.42×10−4) 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=2.47×10−20 for drinker status and beta=−0.19, p=1.91×10−35 for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, p=4.35×10−7 and beta=−0.21, p=2.58×10−6, respectively). While 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=3.41×10−10 for drinks/week and OR=0.96, p=4.08×10−5 for drinker status), and rs4665985 (beta = 0.04, p=2.26×10−8 for drinks/week and OR=1.04, p=5.00×10−4 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.
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影响因子：
7.1
作者：
Baik, Inkyung;Cho, Nam H.;Shin, Chol
通讯作者：
Shin, Chol
影响因子：
3.3
作者：
Kvale, Mark N.;Hesselson, Stephanie;Risch, Neil
通讯作者：
Risch, Neil
DOI：
10.1038/nrgastro.2013.86
发表时间：
2013-08
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1097/00000374-200012000-00011
发表时间：
2000-12-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Dawson, DA
通讯作者：
Dawson, DA
DOI：
10.15288/jsa.2000.61.637
发表时间：
2000-09-01
期刊：
JOURNAL OF STUDIES ON ALCOHOL
影响因子：
--
作者：
Dawson, DA
通讯作者：
Dawson, DA