期刊
MOLECULAR PSYCHIATRY
卷 17, 期 4, 页码 445-450出版社
SPRINGERNATURE
DOI: 10.1038/mp.2011.124
关键词
ADH1B; alcohol dehydrogenase; alcohol dependence; association study; genetics; protective allele
资金
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse [U10 AA008401, R01 DA013423, R01 DA019963]
- National Cancer Institute [P01 CA089392]
- NIDA [K02 DA021237]
A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 x 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P = 3 x 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations. Molecular Psychiatry (2012) 17, 445-450; doi: 10.1038/mp.2011.124; published online 4 October 2011
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