Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations

Background: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this seretonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. Methods: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n = 418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. Results: In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P = .04) and weak evidence with D6S284 (P = .06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-86IC allele frequency than the other 457 Finns we studied (P = .005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P = .01) was again observed, and there was also significant linkage to D6S284 (P = .01). Conclusion: These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.