A polymorphism of the β1-adrenergic receptor is associated with low extraversion

Background: We examined the possibility that allelic variation leading to alterations in beta(1)-adrenergic function might be present in persons with elevated social anxiety-related traits. Methods: A sample of 504 undergraduate college students were phenotyped on a personality inventory (the NEC-Personality Inventory-Revised) and measures of shyness and social anxiety and genotyped for two beta(1) adrenergic (ADRB1 gene) polymorpbisms: a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly). We hypothesized that the Gly49 variant (thought to be functional), but not variation at Arg389Gly, would be associated with (low) extraversion and shyness. We evaluated the potential for population stratification artifact by genotyping a set of 36 unlinked, highly polymorphic markers previously demonstrated to sufficiently distinguish the ancestry of major American populations. Results. Presence of a Gly49 allele was associated with an increased odds of having low or very low extraversion (odds ratio = 1.68, 95% confidence interval 1.05-2.71). The Arg389Gly polymorphism, although in tight linkage disequilibrium (D' = -1.00) with Ser49Gly, was not significantly associated with level of extraveision. Formal testing showed that population structure did not explain the findings. Conclusions: The Ser49Gly functional polymorphism in the beta(1) adrenergic receptor might explain some of the population variance in extraversion and related personality traits. Population structure was excluded as an explanation for these findings. We used a sufficient marker set to exclude possible population stratification artifact. These findings should be replicated and extended to the study of psychiatric disorders marked by low extraversion, namely social phobia and other phobic disorders.