Psychological Medicine



Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors


VALERIE S. KNOPIK a1c1, ANDREW C. HEATH a1, PAMELA A. F. MADDEN a1, KATHLEEN K. BUCHOLZ a1, WENDY S. SLUTSKE a1, ELLIOT C. NELSON a1, DIXIE STATHAM a1, JOHN B. WHITFIELD a1 and NICHOLAS G. MARTIN a1
a1 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Missouri Alcoholism Research Center, Department of Psychological Sciences, University of Missouri, Columbia, MO, USA; Department of Epidemiology and Population Health, Queensland Institute for Medical Research, Brisbane, Australia; Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia

Article author query
knopik vs   [PubMed][Google Scholar] 
heath ac   [PubMed][Google Scholar] 
madden pa   [PubMed][Google Scholar] 
bucholz kk   [PubMed][Google Scholar] 
slutske ws   [PubMed][Google Scholar] 
nelson ec   [PubMed][Google Scholar] 
statham d   [PubMed][Google Scholar] 
whitfield jb   [PubMed][Google Scholar] 
martin ng   [PubMed][Google Scholar] 

Abstract

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk.

Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk.

Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences.

Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.


Correspondence:
c1 Dr Valerie S. Knopik, Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, 40 N. Kingshighway, Suite 1, St. Louis, MO 63108. (Email: vsknopik@matlock.wustl.edu)


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