A dopamine receptor genetic variant enhances perceptual speed in cognitive healthy subjects

INTRODUCTION: Cognition is under strong genetic control, yet the specific genes are unknown. METHODS: One hundred and fifty-three cognitive healthy European subjects from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning). RESULTS: One hundred and fifty-nine variants nominally were found significant in the RANN cohort and re-evaluated in an independent cohort of 868 cognitive healthy subjects from the Religious Orders Study and Rush Memory Aging Project. Meta-analysis yielded a Bonferroni adjusted statistically significant association between perceptual speed and a variant located in the promoter of the dopamine receptor D4 gene, rs3756450 (β = 0.23, standard error = 0.05, P(meta) = 2.3 × 10(−5)). DISCUSSION: Our data suggest that genetic variation in a dopamine pathway gene influences perceptual speed performance in cognitively healthy individuals.