Linkage of Antisocial Alcoholism to the Serotonin 5-HT1B Receptor Gene in 2 Populations

TLDR

Mouse studies implicate the serotonin 5‑HT1B autoreceptor in alcohol consumption and aggressive behavior. The study examined whether the HTR1B gene is linked to antisocial alcoholism in humans, focusing on antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. Linkage was assessed in 640 Finnish subjects and 418 Southwestern American Indian family members by psychiatric interview, blind rating, and genotyping for HTR1B G861C and D6S284, with sib‑pair and pedigree‑randomized association analyses. Finnish antisocial alcoholics showed significant linkage to HTR1B G861C and higher allele frequency, and similar linkage was found in the Southwestern American Indian tribe, indicating that a locus predisposing to antisocial alcoholism is linked to HTR1B at 6q13‑15.

Abstract

<h3>Background</h3> In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene<i>(HTR1B)</i>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. <h3>Methods</h3> 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<i>HTR1B G861C</i>polymorphism and for a closely linked short-tandem repeat locus,<i>D6S284</i>. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. <h3>Results</h3> In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to<i>HTR1B G861C</i>(<i>P</i>=.04) and weak evidence with<i>D6S284</i>(<i>P</i>=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher<i>HTR1B-86IC</i>allele frequency than the other 457 Finns we studied (<i>P</i>=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to<i>HTR1B G861C</i>(<i>P</i>=.01) was again observed, and there was also significant linkage to<i>D6S284</i>(<i>P</i>=.01). <h3>Conclusion</h3> These results suggest that a locus predisposing to antisocial alcoholism may be linked to<i>HTR1B</i>at 6q13-15.