Between- and within-family association test of the dopamine receptor D2 TaqIA polymorphism and alcohol abuse and dependence in a general population sample of adults.
OBJECTIVE
Dopaminergic dysfunction has been hypothesized to play an important role in the etiology of alcohol-use disorders. A restriction fragment length polymorphism (RFLP) in the 3' untranslated region (3'UTR) of the DRD2 gene affects gene expression and has been implicated as a risk factor for alcohol dependence. This polymorphism (TaqIA) has been reported as positively associated with alcohol-use disorders in case-control samples, but these results have not been replicated in family-based association studies. The mixed results of association between the DRD2 TaqIA polymorphism and alcohol-use disorders may be the result of differences in sample size, phenotype definition, heterogeneity of the samples, and genetic admixture.


METHODS
We conducted tests of association in a sample of 838 adults participating in the National Youth Survey Family Study (NYSFS). We examined whether the DRD2 TaqIA polymorphism was associated with a symptom-count measure of alcohol abuse and dependence derived from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Craving Withdrawal Model.


RESULTS
Tests of association were nonsignificant across each classification system examined. Power calculations suggested that these results were despite the ability to detect an effect size of 1%.


CONCLUSIONS
This study supports other family-based association tests that have reported no association between the DRD2 TaqIA polymorphism and alcohol abuse and dependence.
Haberstick
Brett C
BC
Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO 80309-0447, USA. brett.haberstick@colorado.edu
Timberlake
David
D
Smolen
Andrew
A
Sakai
Joseph T
JT
Hopfer
Christian J
CJ
Corley
Robin P
RP
Young
Susan E
SE
Stallings
Michael C
MC
Huizinga
David
D
Menard
Scott
S
Hartman
Christy
C
Grotpeter
Jennifer
J
Hewitt
John K
JK
D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D002648:Child; D003430:Cross-Sectional Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008957:Models, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D014481:United States
D020413:3' Untranslated Regions; D017448:Receptors, Dopamine D2; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases