Alcoholism Susceptibility Loci: Confirmation Studies in a Replicate Sample and Further Mapping

Abstract

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.

A genome wide search for alcoholism susceptibility genes

“…A second region which includes markers D1S196 and D1S2878 is within 1 cM of the gene for an aldehyde dehydrogenase (ALDH9), an enzyme that catalyzes gamma aminobutylaldehyde to GABA. The region near D1S230 has previously been reported by the COGA group to give evidence for linkage Foroud et al, 2000;Nurnberger et al, 2001;Dick et al, 2002]. In the present study, multipoint linkage analysis showed a LOD value of 3.46 (P = 0.002) for marker D1S196 [181.49 cM Marshfield] and a similar LOD value (3.45) at the adjacent marker D1S2878 using a three covariate model that included age, gender, and constraint.…”

“…The chromosome 4 region extended 38 cM near D4S2393 and D4S2361 [69.6 cM] and had a LOD score of 2.50. Results of genotyping a replication sample of 157 COGA families supported the linkage findings for chromosome 1 for marker D1S1588, with the combined sample decreasing to LOD = 2.6 [Foroud et al, 2000]. The linkage reported for chromosome 7 at D7S821 increased in the combined data to LOD = 2.9.…”

“…For chromosome 2, the peak LOD score for the initial sample was 3.0, at marker D2S379 (Marshfield 85.48 cM), a signal that was not maintained in the replication sample. A new finding for chromosome 3 was identified in the replication sample that reached a LOD score of 3.4 [Foroud et al, 2000]. Curiously, there was no discussion of the chromosome 4 finding noted by Reich et al [1998] in the Foroud et al [2000] report.…”

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.…”