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Genome-wide search for genes affecting the risk for alcohol dependence
Authors:Theodore Reich  Howard J. Edenberg  Alison Goate  Jeff T. Williams  John P. Rice  Paul Van Eerdewegh  Tatiana Foroud  Victor Hesselbrock  Marc A. Schuckit  Kathleen Bucholz  Bernice Porjesz  Ting-Kai Li  P. Michael Conneally  John I. Nurnberger  Jay A. Tischfield  Raymond R. Crowe  C. Robert Cloninger  William Wu  Shantia Shears  Kristie Carr  Candice Crose  Chris Willig  Henri Begleiter
Abstract:Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3–8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50–60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:207–215, 1998. © 1998 Wiley-Liss, Inc.
Keywords:linkage analysis  alcoholism  alcohol dependence  genome screening  genetic susceptibility
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