Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence.
BACKGROUND
Alcoholism is a phenotypically and probably genetically heterogeneous condition. Thus, one strategy for finding genes influencing liability to alcoholism is to study the components of alcoholism, which may be more directly related to the underlying pathophysiology than is clinical diagnosis. The goal of this study was to identify genomic regions containing susceptibility loci for alcohol-related traits.


METHODS
A 4-cM dense whole-genome linkage study was conducted in the Irish Affected Sib Pair Study of Alcohol Dependence. Probands, affected siblings, and parents were evaluated by structured interview. Variance component linkage analysis was applied to data from 485 families for 5 measures: initial sensitivity and tolerance (based on scales from the self-report of the effects of ethanol; maximum drinks within 24 hours, an empirically derived factor score based on withdrawal symptoms, and age at onset of alcohol dependence.


RESULTS
Evidence for linkage (p<0.005) was found on 9 chromosomes. For age at onset, 2 regions were found on chromosome 9 (highest Lod=2.3, p=0.0005). For initial level of response to alcohol, suggestive regions were on chromosomes 1 and 11 (highest Lod=2.9, p=0.0001 on chromosome 11), while those for tolerance signals were on chromosomes 1, 6, and 22. Maximum drinking was associated with regions on chromosomes 12 and 18. For withdrawal symptoms, the highest peak was on chromosome 2 (Lod=2.2, p=0.0007).


CONCLUSIONS
Using quantitative measures of components of alcohol dependence, we identified several regions of the genome that may contain susceptibility loci for specific alcohol-related traits and merit additional study.
Kuo
Po-Hsiu
PH
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA. pkuo@vcu.edu
Neale
Michael C
MC
Riley
Brien P
BP
Webb
Bradley Todd
BT
Sullivan
Patrick F
PF
Vittum
Jen
J
Patterson
Diana G
DG
Thiselton
Dawn L
DL
van den Oord
Edwin J
EJ
Walsh
Dermot
D
Kendler
Kenneth S
KS
Prescott
Carol A
CA
D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D010641:Phenotype; D035781:Siblings; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D002492:Central Nervous System Depressants; D000431:Ethanol