Wetherill Leah, Agrawal Arpana, Kapoor Manav, Bertelsen Sarah, Bierut Laura J, Brooks Andrew, Dick Danielle, Hesselbrock Michie, Hesselbrock Victor, Koller Daniel L, Le Nhung, Nurnberger John I, Salvatore Jessica E, Schuckit Marc, Tischfield Jay A, Wang Jen-Chyong, Xuei Xiaoling, Edenberg Howard J, Porjesz Bernice, Bucholz Kathleen, Goate Alison M, Foroud Tatiana
Indiana University School of Medicine, Indianapolis, IN, USA.
Addict Biol. 2015 May;20(3):617-27. doi: 10.1111/adb.12153. Epub 2014 May 16.
Alcohol and drug use disorders are individually heritable (50%). Twin studies indicate that alcohol and substance use disorders share common genetic influences, and therefore may represent a more heritable form of addiction and thus be more powerful for genetic studies. This study utilized data from 2322 subjects from 118 European-American families in the Collaborative Study on the Genetics of Alcoholism sample to conduct genome-wide association analysis of a binary and a continuous index of general substance dependence liability. The binary phenotype (ANYDEP) was based on meeting lifetime criteria for any DSM-IV dependence on alcohol, cannabis, cocaine or opioids. The quantitative trait (QUANTDEP) was constructed from factor analysis based on endorsement across the seven DSM-IV criteria for each of the four substances. Heritability was estimated to be 54% for ANYDEP and 86% for QUANTDEP. One single-nucleotide polymorphism (SNP), rs2952621 in the uncharacterized gene LOC151121 on chromosome 2, was associated with ANYDEP (P = 1.8 × 10(-8) ), with support from surrounding imputed SNPs and replication in an independent sample [Study of Addiction: Genetics and Environment (SAGE); P = 0.02]. One SNP, rs2567261 in ARHGAP28 (Rho GTPase-activating protein 28), was associated with QUANTDEP (P = 3.8 × 10(-8) ), and supported by imputed SNPs in the region, but did not replicate in an independent sample (SAGE; P = 0.29). The results of this study provide evidence that there are common variants that contribute to the risk for a general liability to substance dependence.
酒精和药物使用障碍具有个体遗传性（50%）。双生子研究表明，酒精和物质使用障碍具有共同的遗传影响，因此可能代表一种遗传性更强的成瘾形式，从而在基因研究中更具效力。本研究利用来自酒精中毒遗传学合作研究样本中118个欧美家庭的2322名受试者的数据，对一般物质依赖易感性的二元指标和连续指标进行全基因组关联分析。二元表型（ANYDEP）基于符合《精神疾病诊断与统计手册》第四版（DSM-IV）中对酒精、大麻、可卡因或阿片类物质任何一种的终身依赖标准。定量性状（QUANTDEP）是基于对四种物质各自的七个DSM-IV标准的认可，通过因子分析构建而成。ANYDEP的遗传度估计为54%，QUANTDEP为86%。一个单核苷酸多态性（SNP），即位于2号染色体上未表征基因LOC151121中的rs2952621，与ANYDEP相关（P = 1.8 × 10⁻⁸），周围的推断SNP提供了支持，并在一个独立样本[成瘾：遗传学与环境研究（SAGE）]中得到验证（P = 0.02）。一个SNP，即ARHGAP28（Rho GTP酶激活蛋白28）中的rs2567261，与QUANTDEP相关（P = 3.8 × 10⁻⁸），该区域的推断SNP提供了支持，但在一个独立样本（SAGE；P = 0.29）中未得到验证。本研究结果提供了证据，表明存在一些常见变异体，它们会增加一般物质依赖易感性的风险。
