Genome-wide search for genes affecting the risk for alcohol dependence

TLDR

Alcohol dependence causes significant morbidity and premature death, and genetic factors contribute substantially, with family and twin studies indicating a 3–8 fold increased risk and 50–60 % heritability. The study aimed to identify genetic loci associated with alcohol dependence through a multi‑center collaboration. The authors performed a genome‑wide linkage scan of 291 markers in 987 individuals from 105 families, using two‑point and multipoint nonparametric linkage analyses to detect susceptibility loci. Multipoint linkage analysis identified strong linkage signals on chromosomes 1 and 7, modest evidence on chromosome 2, and a suggestive protective locus near alcohol dehydrogenase genes on chromosome 4.

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.