Polymorphism of the 5-HT1B receptor gene (HTR1B): Strong within-locus linkage disequilibrium without association to antisocial substance dependence

Serotonergic abnormalities may be present in individuals with either substance dependence (SD) or antisocial personality disorder (ASPD), disorders that occur together commonly. Consequently, genes encoding serotonin (5-HT) receptors are candidates for genetic studies of both disorders. Lappalainen et al. (1998) found evidence for linkage of antisocial alcoholism to HTR1B (the locus encoding the 5-HT1B receptor) in both Finns and Southwestern American Indians, and of allelic association of a G861C polymorphism at that locus with antisocial alcoholism in Finns, Unless the G861C polymorphism is found to be functional, it must be in linkage disequilibrium (LD) with a functional variant for it to be of physiological significance. Methods: The present study evaluated LD across three polymorphic systems at HTR1B and haplotype frequencies and allelic association of these systems with both SD generally and alcohol dependence (AD) specifically, with or without a comorbid antisocial diagnosis. Subjects were 370 European Americans (EAs) and 123 African Americans (AAs). Results: Although there was strong evidence for LD across polymorphic systems in both populations, there was no evidence for association to SD or AD, either alone or with a comorbid antisocial diagnosis. Conclusion: Despite no evidence in this study for allelic association of HTR1B to antisocial substance dependence, further evaluation of the hypothesized association is warranted in other population groups. [Neuropsychopharmacology 26:115-122, 2002] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.