Impact of the dopamine receptor gene family on temperament traits in a population-based birth cohort.

Although the genetic determinants of personality have been intensively investigated especially since Cloninger proposed his psychobiological model of temperament and character, findings to date remain inconclusive and very few studies have addressed the topic in large population cohorts. In the current study we investigated one gene family in its entirety by addressing the role of all known dopamine receptor genes, DRD1-DRD5, on Cloninger's temperament traits in a Finnish population-based birth cohort. The study sample (n = 1,434) was ascertained from the Northern Finland Birth Cohort 1966 with over 5,000 study individuals tested at the age of 31 years. We utilized the genetic homogeneity and genealogical structure of this population to uncover putative effects of these genes on temperament traits at the population level. Our strategy utilizing a large birth cohort and its well established genealogical structure represents an optimal design for studying normally distributed traits. We also wished to provide a comprehensive view to one biologically relevant gene family instead of testing single candidate genes. We report evidence of association of several SNPs at the 5' end of dopamine receptor D2 (DRD2) with Novelty seeking (low) and Harm avoidance (high), and at the 3' end of DRD2 with Persistence. The strongest evidence of association emerged from females. Our study supports the involvement of the dopamine pathway in temperament traits, in particular underlining the role of DRD2 in Novelty seeking, Harm avoidance and Persistence. (c) 2008 Wiley-Liss, Inc.