No association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore longitudinal study of aging participants

Recent studies by Ebstein et al¹ and Benjamin et al² found associations between long repeat polymorphisms in the D4 dopamine receptor gene (D4DR) and individual variation in a human personality trait, identified as 'Novelty Seeking'(NS). Ebstein et al used the Tridimensional Personality Questionnaire (TPQ)³ to measure NS scores; Benjamin et al used the Revised NEO Personality Inventory (NEO-PI-R)⁴ to estimate NS scores. However, Malhotra et al⁵ failed to replicate the association between the direct measure of NS using the TPQ and the long alleles of the D4DR genotypes in two Finnish samples. In an attempt to confirm the association found by Benjamin et al using NEO-PI-R estimated NS, the present study used an alternative design extreme groups strategy to select high and low novelty seeking research volunteers from the Baltimore Longitudinal Study of Aging (BLSA).⁶ There were no significant associations between long alleles (7-repeat allele) and high novelty seeking groups. The findings of Ebstein and colleagues and those of Benjamin and colleagues do not generalize to this American middle-aged, mixed-gender sample, a conclusion also consistent with the findings of a recent Swedish study.⁷ Demographic factors such as the age and gender composition of the samples are important sources of variation in allelic association studies and future research must carefully address whether the D4DR genetic polymorphisms vary substantially across demographic groups.