LINKAGE OF ANTISOCIAL ALCOHOLISM TO THE SEROTONIN 5-HT1B RECEPTOR GENE IN 2 POPULATIONS

Background: In mice, quantitative trait locus studies and behavioral e valuation of animals deleted for 5-HT1B have implicated this seretonin autoreceptor in alcohol consumption and aggressive behavior. We there fore investigated whether the 5-HT1B gene (HTR1B) is linked to alcohol ism with aggressive and impulsive behavior in the human, as represente d by 2 psychiatric diagnoses: antisocial personality disorder and inte rmittent explosive disorder comorbid with alcoholism. Methods: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic cri minal offenders, 261 relatives, and 213 healthy controls. This was fol lowed by a study in a large multigenerational family derived from a So uthwestern American Indian tribe (n = 418) with a high rate of alcohol ism. All subjects were psychiatrically interviewed, blind-rated for ps ychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evalua ted in sib pairs, and by using an association approach in which pedigr ee randomization corrects for nonindependence of observations on relat ed subjects. Results: In Finnish sib pairs, antisocial alcoholism show ed significant evidence of linkage to HTR1B G861C (P = .04) and weak e vidence with D6S284 (P = .06). By association analysis, the 183 Finnis h antisocial alcoholics had a significantly higher HTR1B-86IC allele f requency than the other 457 Finns we studied (P = .005). In the Southw estern American Indian tribe, significant sib pair linkage of antisoci al alcoholism to HTR1B G861C (P = .01) was again observed, and there w as also significant linkage to D6S284 (P = .01). Conclusion: These res ults suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.