Human personality traits are strong predictors or characteristics of many psychiatric disorders including substance dependence (SD). Recently, significant associations between alcohol dehydrogenase type 1A gene (ADH1A) and SD have been reported, which led us to investigate the impact of ADH1A variation on personality traits and risk of SD. Five hundred fifty-eight subjects with SD [398 European-Americans (EAs) and 160 African-Americans (AAs)], 517 college students (384 EAs and 133 European-origin Hispanics), and 448 healthy subjects (385 EAs, 48 AAs, and 15 European-origin Hispanics) participated. Personality traits were assessed in 247 subjects with SD (179 EAs and 68 AAs), all 517 college students, and 332 healthy subjects (285 EAs, 40 AAs, and 7 European-origin Hispanics). The relationships between ADH1A and personality traits were comprehensively examined using stepwise multivariate analysis of covariance (MANCOVA), and then decomposed by stepwise analysis of covariance (ANCOVA). The relationship between ADH1A and SD was examined using stepwise logistic regression analysis. Admixture effects on analyses were considered. Overall, Agreeableness and Conscientiousness were associated with the diplotypes, haplotypes, genotypes, and/or alleles of ADH1A in three of four phenotype groups including EA SD subjects, healthy subjects, and AA SD subjects (1.7 x 10(-4) <or= P <or= 0.055), but not college students. Neuroticism was associated with diplotype, haplotypes and genotypes in AA SD subjects (0.001 <or= P <or= 0.031). In addition, SD was associated with diplotypes, haplotypes, genotypes, and/or alleles of ADH1A (0.008 <or= P <or= 0.060). The present study demonstrates that the ADH1A variation may contribute to the genetic component of variation in personality traits and SD.
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