Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans

Abstract

Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with seven alcohol dehydrogenase (ADH) genes. The present study examines the relationship between these genes and DD. We genotyped 16 markers within the ADH gene cluster and 38 unlinked ancestry-informative markers in a case-control sample of 718 individuals. All markers were consistent with Hardy-Weinberg equilibrium in controls, but some markers showed Hardy-Weinberg disequilibrium in cases (minimal P = 0.002). Genotypes of many markers were associated with DD, both before and after controlling for admixture effects (minimal P < 1.0 x 10(-6)). Diplotype trend regression analysis showed that ADH5 and ADH6 genotypes, and diplotypes at ADH1A, ADH1B, ADH1C and ADH7 (minimal P = 0.002), were associated with DD in European-Americans and/or African-Americans. This first report of an allelic association of these loci with DD provides new insight into the mechanism of genetic risk for DD. These findings, obtained using a series of powerful and reliable analytic methods, may also help to explain the high rate of co-morbidity between AD and DD.

Genetics and alcoholism

“…There are smaller effects of variants in other alcohol dehydrogenases, particularly ADH1C and ADH4 † , and reports of modest effects of other aldehyde dehydrogenase genes 20, 33, 38-40 . However, studies have been complicated by the fact that many variants among the ADH genes are in significant linkage disequilibrium (co-inherited).…”

Genetic pre-determinants of concurrent alcohol and opioid dependence: A critical review

“…Two SNPs were more likely to be associated with concurrent drug and alcohol dependence in European Americans (ADH5 rs1154400, ADH7 rs1573496), compared to drug dependence alone (21). One SNP was associated with concurrent drug and alcohol dependence in African Americans (ADH1C rs1693482) and one SNP was associated with concurrent drug and alcohol dependence in both populations (ADH1B rs1229984) (21).…”

“…A total of seven ADH genes (ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, and ADH7) were analysed in two separate studies (20,21). It is important to note that this was a recessive association.…”

Developing a Quantitative Measure of Alcohol Consumption for Genomic Studies on Prospective Cohorts

“…Stud. Alcohol Drugs 70: [157][158][159][160][161][162][163][164][165][166][167][168]2009) M EASURES OF SUBSTANCE-USE PROBLEMS as defi ned by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994), are becoming more widely applied in genomic studies (e.g., Edenberg et al, 2004;Gelernter et al, 2005Gelernter et al, , 2006Luo et al, 2007;Uhl et al, 2001). The popularity of such measures may stem, in part, from the possible clinical implications of discovering genomic regions associated with a psychiatric disorder as defi ned by established criteria.…”