Reich T, Edenberg H J, Goate A, Williams J T, Rice J P, Van Eerdewegh P, Foroud T, Hesselbrock V, Schuckit M A, Bucholz K, Porjesz B, Li T K, Conneally P M, Nurnberger J I, Tischfield J A, Crowe R R, Cloninger C R, Wu W, Shears S, Carr K, Crose C, Willig C, Begleiter H
Department of Psychiatry, Washington University, St. Louis, Missouri 63110, USA.
Am J Med Genet. 1998 May 8;81(3):207-15.
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.
酒精依赖是发病和过早死亡的主要原因。多项证据表明，酗酒风险存在很大的遗传因素：酗酒先证者的兄弟姐妹患酗酒症的风险增加3至8倍，当代双胞胎研究报告的双胞胎遗传率估计为50%至60%。我们报告了一项六中心合作研究的结果，该研究旨在确定酒精依赖的易感基因座。一项全基因组筛查检测了来自105个家庭的987名个体中的291个标记。进行了两点和多点非参数连锁分析，以检测酒精依赖的易感基因座。多点方法最有力地表明了与1号和7号染色体上酒精依赖易感基因座的连锁关系，对2号染色体上一个基因座的证据则相对较弱。此外，有暗示性证据表明，在靠近酒精脱氢酶基因的4号染色体上存在一个保护性基因座，亚洲人群中曾报告过该基因座的保护作用。
