Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is thought to influence emotion. A 5-HTT-linked polymorphic region (5-H TTLPR) has two common variants, short (s) and long (1). We previously found population and within-family associations between the lower-expressing s a llele and neuroticism, a trait related to anxiety, hostility, and depressio n, on a standard measure (the NEO Personality Inventory, Revised [NEO-PI-R] ) in a primarily male population (n = 505), and that the s allele was domin ant. We investigated this association in a new sample (n = 397, 84% female, primarily sib-pairs). The results robustly replicated the 5-HTTLPR neuroti cism association, and the dominance of the s allele. Combined data from the two studies (n = 902) showed a highly significant association between the s allele and higher NEO Neuroticism both across individuals and within fami lies. Association between genotype and a related measure, Anxiety on the 16 PF inventory, was replicated in the new population and within families in t he combined sample. Association to another trait, estimated TPQ Harm Avoida nce, was not replicated in the new sample but found only within the combine d sibship group. Another association found in our original study, between t he s allele and lower scores on NEO-PI-R Agreeableness, was also replicated and was more robust in the current and the combined samples. Associations between the functional 5-HTTLPR polymorphism were similar in women and men. These results help to define specific personality features reproducibly as sociated with 5-HTTLPR genotype. Such associations were strongest for trait s defined by the NEO, enhancing the attractiveness of the five-factor perso nality model in genetic research on complex behavioral dimensions. (C) 2000 Wiley-Liss, Inc.