Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk
Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk
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DOI：
10.1111/j.1360-0443.2007.01871.x
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发表时间：
2007-07-01
期刊：
影响因子：
6
通讯作者：
Bierut, Laura J.
中科院分区：
文献类型：
--
作者：
Dick, Danielle M.;Agrawal, Arpana;Bierut, Laura J.
背景：双数据表明，酒精依赖与非法药物依赖合并症是一种更易遗传的疾病形式。在酒精中毒遗传样本的合作研究中，大约一半的酒精依赖者也符合非法药物依赖的诊断标准。在这项研究中，我们测试了毒蕈碱乙酰胆碱M2受体基因（CHRM2）与酒精依赖之间的异质性，之前在全样本中报道，在有或没有共病药物依赖的酒精依赖个体亚组中。方法分别对酒精依赖合并合并药物依赖的个体（n = 477）和酒精依赖合并合并药物依赖的个体（n = 433）进行基于家庭的关联检验。这些亚组随后进行了其他表型特征的比较。结果CHRM2与酒精依赖相关的证据完全来自共病药物依赖个体亚组。在没有药物依赖的酒精依赖个体中，没有证据表明与CHRM2相关。随后的表型分析表明，伴有共病药物依赖的酒精依赖个体亚组在许多其他表型特征上存在差异，包括酒精问题严重程度、人格特征和共病精神障碍的几种测量方法。这些分析提供了特定的遗传证据，表明酒精依赖与共病药物依赖是一种特别严重的疾病形式，遗传因素对易感性的贡献更高。
Background Twin data suggest that alcohol dependence comorbid with illicit drug dependence represents a more heritable form of the disorder. In the Collaborative Study on the Genetics of Alcoholism sample, approximately half the alcohol-dependent individuals also meet diagnostic criteria for illicit drug dependence. In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence. Methods Family-based association tests were conducted separately (a) in individuals with alcohol dependence with comorbid drug dependence (n = 477) and (b) in individuals with alcohol dependence without comorbid drug dependence (n = 433). These subgroups were subsequently compared on other phenotypic characteristics. Results The evidence for association between CHRM2 and alcohol dependence came entirely from the subgroup of individuals with comorbid drug dependence. There was no evidence of association with CHRM2 among the alcohol-dependent individuals without drug dependence. Subsequent phenotypic analyses suggest that the subgroup of alcohol-dependent individuals with comorbid drug dependence differ on a number of other phenotypic characteristics, including several measures of the severity of their alcohol problems, personality traits and comorbid psychiatric disorders. Conclusions These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.