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

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.

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics

“…20,21 This association was recently supported by a family-based study using genetic fine-mapping of the 1p region of chromosome 1. 29 Comparing gentoype frequencies in our study with previous research (Begni et al, 30 30 who reported lower genotype frequencies of the GRIK3 polymorphism Ser allele in his sample of schizophrenic patients.…”

“…18 The GluR7 subunit of KA receptors has been mapped to chromosome 1 at 1p34-p33, 19 close to a region reported to be associated with alcoholism and alcoholism-related phenotypes from linkage studies. [20][21][22] GluR7 receptor subunits form a functional homomeric receptor channel with low sensitivity to glutamate. 23 The GluR7 contains an exonic thymine/guanine nucleotide variation that determines a serine or alanine at position 310 in the N-terminal extracellular domain of the receptor.…”

Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

“…Although genetic etiology for alcohol use and dependence has been well supported (Wolff, 1972; Heath et al, 1997; Reich et al, 1998; Madden et al, 2000; Madden and Heath, 2002; Schuckit, 2009), much work remains to elucidate particular genetic risk mutations and understand genetic mechanisms. Alcohol genetic studies have focused primarily on alcohol dehydrogenases and related genes, and also on gamma-amiobutyric acid ( GABA ) genes.…”

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

“…Although classical genetic studies, such as twin and adoption studies, estimated the genetic contribution to alcoholism as approximately 0.5, 1-3 few family-based linkage studies have yielded consistent linkages at specific loci. [4][5][6][7] The genetic polymorphisms in the alcohol metabolizing pathway, such as aldehyde dehydrogenase 2 (ALDH2) 8 and alcohol dehydrogenase (ADH) [9][10][11][12] appear to be associated with alcoholism vulnerability. Aside from the genes encoding the metabolizing enzyme, there appear to be no single gene that plays a significant role in alcoholism, and small functional gene effects may act in conjunction with environmental factors to promote alcoholism.…”