Department of Psychiatry , Yale University School of Medicine, New Haven, Connecticut.
Department of Psychiatry , VA Connecticut Healthcare System, West Haven, Connecticut.
Alcohol Clin Exp Res. 2018 May;42(5):861-868. doi: 10.1111/acer.13614. Epub 2018 Mar 13.
Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations. Similarly, variants mapped to these same genes and a well-known null variant that maps to the gene that encodes aldehyde dehydrogenase 2 (ALDH2) also affect risk in various Asian populations. In this study, we completed the first GWAS for 3 traits related to alcohol use in a Thai population recruited initially for studies of methamphetamine dependence.
All subjects were evaluated with the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). A total of 1,045 subjects were available for analysis. Three traits were analyzed: flushing, maximum number of alcoholic beverages consumed in any lifetime 24-hour period ("MAXDRINKS"), and DSM-IV alcohol dependence criterion count. We also conducted a pleiotropy analysis with major depression, the only other psychiatric trait where summary statistics from a large-scale Asian-population GWAS are available.
All 3 traits showed genomewide significant association with variants near ALDH2, with significance ranging from 2.01 × 10 (for flushing; lead single nucleotide polymorphism (SNP) PTPN11* rs143894582) to p = 5.80 × 10 (for alcohol dependence criterion count; lead SNP rs149212747). These lead SNPs flank rs671 and span a region of over a megabase, illustrating the need for prior biological information in identifying the actual effect SNP, rs671. We also identified significant pleiotropy between major depression and flushing.
These results are consistent with prior findings in Asian populations and add new information regarding alcohol use-depression pleiotropy.
饮酒（包括饮酒量和依赖程度）具有中等程度的遗传性，全基因组关联研究（GWAS）已经在欧洲、非洲和亚洲人群中鉴定出了风险基因。最具可重复性的风险基因会影响酒精代谢。在编码醇脱氢酶 B 和其他醇脱氢酶的基因中发现的知名功能变体影响着欧洲和非洲血统人群的风险。同样，映射到这些相同基因的变体以及映射到编码乙醛脱氢酶 2（ALDH2）的已知无效变体也会影响各种亚洲人群的风险。在这项研究中，我们完成了第一项针对泰国人群中与饮酒相关的 3 个特征的 GWAS，该人群最初是为研究冰毒依赖而招募的。
所有受试者均接受了泰国版半结构化药物依赖和酒精中毒评估（SSADDA）的评估。共有 1045 名受试者可用于分析。分析了 3 个特征：潮红、一生中任何 24 小时内最多饮用的酒精饮料数量（“MAXDRINKS”）和 DSM-IV 酒精依赖标准计数。我们还进行了与重度抑郁症的多效性分析，这是唯一其他具有大规模亚洲人群 GWAS 汇总统计数据的精神疾病特征。
所有 3 个特征均与 ALDH2 附近的变体显示出全基因组显著关联，其显著性范围从潮红（lead single nucleotide polymorphism [SNP] PTPN11*rs143894582）的 2.01×10 -8 到酒精依赖标准计数（lead SNP rs149212747）的 p=5.80×10 -8。这些 lead SNP 侧翼是 rs671，跨越超过一个兆碱基的区域，说明了在确定实际效应 SNP rs671 时需要事先的生物学信息。我们还发现了重度抑郁症和潮红之间的显著多效性。
这些结果与亚洲人群中的先前发现一致，并提供了关于饮酒-抑郁多效性的新信息。
