ADH7 variation modulates extraversion and conscientiousness in substance-dependent subjects.

Human personality traits have been closely linked to substance dependence (SD), and are partially genetically determined. Recently, associations between alcohol dehydrogenase 7 (ADH7) and SD have been reported, which led us to investigate the relationship between ADH7 variation and personality traits. We assessed dimensions of the five-factor model of personality and genotyped 4 ADH7 markers and 38 unlinked ancestry-informative markers in 244 subjects with SD [178 European-Americans (EAs) and 66 African-Americans (AAs)] and 293 healthy subjects (253 EAs and 40 AAs). The relationships between ADH7 markers and personality traits were comprehensively examined using multivariate analysis of covariance (MANCOVA), and then decomposed by Roy Bargmann Stepdown analysis of covariance (ANCOVA). Generally, older individuals, AAs, and males had significantly lower personality scores (4.7 x 10(-5) < or = P < or = 0.032), as reported previously. In SD subjects, Extraversion was most significantly associated with ADH7 haplotypes (3.7 x 10(-4) < or = P < or = 0.001), diplotypes (0.007 < or = P < or = 0.012), and genotypes (P = 0.001), followed by Conscientiousness (0.005 < or = P < or = 0.033). The contributory haplotype and diplotypes contained the alleles and genotypes of rs284786 (SNP1) and rs1154470 (SNP4). In healthy subjects, other personality factors (except Extraversion) were associated with ADH7 diplotypes (0.005 < or = P < or = 0.016) and genotypes (0.002 < or = P < or = 0.052). Some of the gene effects on personality factors were modified by sex. The present study demonstrated that the ADH7 variation may contribute to the genetic component of variation in personality traits, with the risk for SD and personality traits being partially shared.