期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 165, 期 4, 页码 294-302出版社
WILEY
DOI: 10.1002/ajmg.b.32231
关键词
AUD; alcohol dependence; variance components linkage analysis; pleiotropy; endophenotype ranking value (ERV); SNP association
资金
- National Institute of Mental Health [MH0708143, MH078111, MH083824, MH59490]
- NIAAA [AA015973, AA11330]
- National Center for Research Resources, National Institutes of Health [C06 RR13556, C06 RR017515]
- ATT Foundation
- National Center for Research Resources [S10 RR029392]
Linkage studies of alcoholism have implicated several chromosome regions, leading to the successful identification of susceptibility genes, including ADH4 and GABRA2 on chromosome 4. Quantitative endophenotypes that are potentially closer to gene action than clinical endpoints offer a means of obtaining more refined linkage signals of genes that predispose alcohol use disorders (AUD). In this study we examine a self-reported measure of the maximum number of drinks consumed in a 24-hr period (abbreviated Max Drinks), a significantly heritable phenotype (h(2) = 0.32 +/- 0.05; P = 4.61 x 10(-14)) with a strong genetic correlation with AUD (rho(g) = 0.99 +/- 0.13) for the San Antonio Family Study (n = 1,203). Genome-wide SNPs were analyzed using variance components linkage methods in the program SOLAR, revealing a novel, genome-wide significant QTL (LOD = 4.17; P = 5.85 x 10(-6)) for Max Drinks at chromosome 6p22.3, a region with a number of compelling candidate genes implicated in neuronal function and psychiatric illness. Joint analysis of Max Drinks and AUD status shows that the QTL has a significant non-zero effect on diagnosis (P = 4.04 x 10(-3)), accounting for 8.6% of the total variation. Significant SNP associations for Max Drinks were also identified at the linkage region, including one, rs7761213 (P = 2.14 x 10(-4)), obtained for an independent sample of Chinese families. Thus, our study identifies a potential risk locus for AUD at 6p22.3, with significant pleiotropic effects on the heaviness of alcohol consumption that may not be population specific. (C) 2014 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据