The search for genes related to a low-level response to alcohol determined by alcohol challenges.
BACKGROUND
A low level of response (LR) to alcohol seems to relate to a substantial proportion of the risk for alcoholism and to have significant heritability.


METHODS
This report describes the results of a genome-wide segregation analysis for the first 139 pairs of full siblings by using an alcohol challenge protocol as a direct measure of LR. Subjects from 18 to 29 years old were selected if the original screen indicated they had an alcohol-dependent parent, reported a personal history of drinking but had no evidence of alcohol dependence, and had a full sibling with similar characteristics. Body sway and Subjective High Assessment Scale scores were measured at baseline and at regular intervals after the administration of a measured dose of alcohol. Participants and available parents were genotyped for 811 microsatellite markers, and resulting data were analyzed with a variance component method.


RESULTS
Nine chromosome regions with logarithm of the odds ratio (LOD) between 2.2 and 3.2 were identified; several had previously been implicated regarding phenotypes relevant to alcoholism and the LR to alcohol. Several regions identified in the previous linkage study by using a retrospective self-report questionnaire were potentially confirmed by this study. The strongest evidence was on chromosomes 10, 11, and 22.


CONCLUSIONS
Several chromosomal areas seem to relate to the low LR to alcohol as a risk factor for alcohol dependence.
Wilhelmsen
Kirk C
KC
Ernest Gallo Clinic and Research Center, Emeryville, California, USA. kirk@egcrc.net
Schuckit
Marc
M
Smith
Tom L
TL
Lee
James V
JV
Segall
Samantha K
SK
Feiler
Heidi S
HS
Kalmijn
Jelger
J
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008040:Genetic Linkage / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype
D000431:Ethanol