Alcoholism susceptibility loci: Confirmation studies in a replicate sample and further mapping

被引:182
作者
Foroud, T
Edenberg, HJ
Goate, A
Rice, J
Flury, L
Koller, DL
Bierut, LJ
Conneally, PM
Nurnberger, JI
Bucholz, KK
Li, TK
Hesselbrock, V
Crowe, R
Schuckit, M
Porjesz, B
Begleiter, H
Reich, T
机构
[1] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
[2] Washington Univ, Sch Med, St Louis, MO USA
[3] Univ Connecticut, Sch Med, Farmington, CT USA
[4] Univ Iowa, Sch Med, Iowa City, IA 52242 USA
[5] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA
[6] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA
来源
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH | 2000年 / 24卷 / 07期
关键词
alcoholism; nonparametric linkage analysis; sibling pair; susceptibility genes;
D O I
10.1097/00000374-200007000-00001
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Background: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. Methods: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. Results: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). Conclusions: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.
引用
收藏
页码:933 / 945
页数:13
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