Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men
Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men
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DOI：
10.3945/ajcn.110.001776
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发表时间：
2011-04-01
影响因子：
7.1
通讯作者：
Shin, Chol
中科院分区：
文献类型：
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作者：
Baik, Inkyung;Cho, Nam H.;Shin, Chol
背景资料：全基因组关联（GWA）研究酒精consumption.Objective的数量性状：本研究的目的是探索与酒精consumption.Design的数量相关的遗传位点：我们进行了一项GWA研究，发现数据单核苷酸多态性（SNP）的1721名韩国男性饮酒者，年龄在40-69 y谁被列入城市人口为基础的队列。另一个样本，包括1113名男性饮酒者谁是从一个独立的队列登记在农村地区作为复制的资源。基线时（2001年6月18日至2003年1月29日），两个队列的成员提供了平均每日饮酒量的信息，并收集了他们的DNA样本进行基因分型。我们使用多变量线性回归分析对发现数据的315，914个SNP进行了测试，并对年龄和吸烟进行了调整，染色体12 q24上的12个SNPs与饮酒量在全基因组范围内具有显著相关性;使用Bonferroni校正的校正P值为1.6 x 10（-5）至5.8 x 10（-46）。我们在内含子区域观察到大多数SNP，并显示具有SNP的基因是C12 orf 51，CCDC 63，MYL 2，OAS 3，CUX 2和RPH 3A。特别是，信号中或附近的C12 orf 51，CCDC 63，和MYL 2被成功地复制在测试中的317，951单核苷酸多态性; rs 2074356在C12 orf 51是在高连锁不平衡与单核苷酸多态性ALDH2.Conclusions的，但其他单核苷酸多态性没有：在GWA研究中，我们确定了基因座和等位基因高度相关的酒精消费。研究结果表明，需要进一步研究饮酒过量的遗传倾向。美国临床营养杂志2011; 93：809-16。
Background: Genome-wide association (GWA) studies regarding the quantitative trait of alcohol consumption are limited.Objective: The objective of the study was to explore genetic loci associated with the amount of alcohol consumed.Design: We conducted a GWA study with discovery data on single nucleotide polymorphisms (SNPs) for 1721 Korean male drinkers aged 40-69 y who were included in an urban population-based cohort. Another sample that comprised 1113 male drinkers who were from an independent cohort enrolled in a rural area served as a resource for replication. At baseline (18 June 2001 through 29 January 2003), members of both cohorts provided information on average daily alcohol consumptions, and their DNA samples were collected for genotyping.Results: We tested 315,914 SNPs of discovery data by using multivariate linear regression analysis adjusted for age and smoking, and 12 SNPs on chromosome 12q24 had genome-wide significant associations with alcohol consumption; adjusted P values by using Bonferroni correction were 1.6 x 10(-5) through 5.8 x 10(-46). We observed most SNPs in intronic regions and showed that the genes that harbor SNPs were C12orf51, CCDC63, MYL2, OAS3, CUX2, and RPH3A. In particular, signals in or near C12orf51, CCDC63, and MYL2 were successfully replicated in the test for 317,951 SNPs; rs2074356 in C12orf51 was in high linkage disequilibrium with SNPs in ALDH2, but other SNPs were not.Conclusions: In a GWA study, we identified loci and alleles highly associated with alcohol consumption. The findings suggest the need for further investigations on the genetic propensity for drinking excessive amounts of alcohol. Am J Clin Nutr 2011; 93: 809-16.