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Alcoholism Susceptibility Loci: Confirmation Studies in a Replicate Sample and Further Mapping
Author(s) -
Foroud Tatiana,
Edenberg Howard J.,
Goate Alison,
Rice John,
Flury Leah,
Koller Daniel L.,
Bierut Laura J.,
Conneally P. Michael,
Nurnberger John I.,
Bucholz Kathleen K.,
Li TingKai,
Hesselbrock Victor,
Crowe Raymond,
Schuckit Marc,
Porjesz Bernice,
Begleiter Henri,
Reich Theodore
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb04634.x
Subject(s) - genetics , genotyping , linkage (software) , biology , genetic linkage , pedigree chart , chromosome , complete linkage , genotype , single nucleotide polymorphism , gene
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.