title: 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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D000426:Alcohol Dehydrogenase