The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity:: Within-family association and linkage analyses
The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity:: Within-family association and linkage analyses
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DOI：
10.15288/jsad.2007.68.625
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Hill, Shirley Y.
中科院分区：
文献类型：
--
作者：
Matthews, Abigail G.;Hoffman, Eric K.;Hill, Shirley Y.
目的：编码γ-氨基丁酸(GABAA)受体的基因是最近几个研究酒精依赖遗传病因的焦点。利用家庭内关联性测试和其他方法，对多个家庭的分析发现，一个特定的基因GABRA2与酒精依赖高度相关。结果在三个病例对照研究中得到证实。本研究的目的是研究另一个多基因家系中的GABRA2基因。方法：对来自两代65个家系的330名个体的表型和基因数据进行分析，共232名酒精依赖者。符合《精神疾病诊断和统计手册》第三版酒精依赖标准的同性兄弟姐妹先证者才能进入研究。先证者对中的一名成员是在接受酒精依赖治疗时被确认的。GABRA2与酒精依赖的连锁和关联分别使用SIBPAL(一个非参数连锁软件包)、系谱不平衡检验和基于家族的关联检验进行评估。结果：我们没有发现GABRA2与酒精依赖有关的证据。使用受影响/受影响、受影响/未受影响和未受影响/未受影响的同胞对(所有p
Objective: The genes encoding the gamma-aminobutyric acid, (GABA A) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Method: Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. Results: We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/ unaffected sib pairs (all p's