Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population.
Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population.
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DOI：
10.1111/acer.13614
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Kalayasiri R
中科院分区：
文献类型：
--
作者：
Gelernter J;Zhou H;Nuñez YZ;Mutirangura A;Malison RT;Kalayasiri R
酒精使用（数量和依赖性）是中度遗传的，全基因组关联研究（GWAS）已经确定了欧洲，非洲和亚洲人群的风险基因。最可重复识别的风险基因影响酒精代谢。众所周知的功能变异基因编码乙醇脱氢酶B（ADH 1 B）和其他乙醇脱氢酶影响欧洲和非洲血统人群的风险。类似地，映射到这些相同基因的变体和映射到编码醛脱氢酶2（ALDH 2）的基因的众所周知的无效变体也影响各种亚洲人群的风险。在这项研究中，我们完成了第一个GWAS的三个性状相关的酒精使用在泰国人口最初招募的甲基苯丙胺依赖性的研究。所有受试者均采用泰国版药物依赖和酒精中毒半结构化评估（SSADDA）进行评估。共有1045例受试者可用于分析。分析了三个特征：潮红、一生中任何24小时内饮用的最大酒精饮料数量（“MAXDRINKS”）和DSM-IV酒精依赖标准计数。我们还对重性抑郁症进行了多效性分析，重性抑郁症是唯一一个可以从大规模亚洲人群GWAS中获得汇总统计数据的其他精神病学特征。所有这三个性状都显示出与ALDH 2附近变异的全基因组显著关联，显著性范围从2.01×10−14（潮红;前导SNP PTPN 11 * rs 143894582）到pmeta = 5.80 × 10−10（酒精依赖标准计数;前导SNP rs 149212747）。这些前导SNP位于rs671的侧翼，跨越超过1兆碱基的区域，说明在鉴定实际效应SNP rs671时需要先验生物学信息。我们还确定了重大抑郁症和潮红之间的显着多效性。这些结果与之前在亚洲人群中的发现一致，并增加了关于酒精使用抑郁多效性的新信息。
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 (ADH1B) 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 three 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 1045 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 three traits showed genomewide-significant association with variants near ALDH2, with significance ranging from 2.01×10−14 (for flushing; lead SNP PTPN11* rs143894582) to pmeta = 5.80 × 10−10 (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.
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影响因子：
11
作者：
Chang JS;Hsiao JR;Chen CH
通讯作者：
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影响因子：
7.6
作者：
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影响因子：
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作者：
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