Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism

In 1996, Ebstein et al. and Benjamin et al, reported significant associations between the long repeat allele of DRD4 exon III and novelty seeking, which is a personality dimension postulated by Cloninger. Because their studies are the first reports that specific genetic polymorphism might influence a normal dimension of personality, a number of replication studies have been conducted to obtain further confirmation of the association. However, it remains unclear whether the initial finding is replicable. The failure to confirm this association is possibly explained by the methodological differences of subsequent studies. Because the estimated size of the DRD4 polymorphism on novelty seeking (NS) explains 3%-4% of the total variance, the noise generated by methodological differences may be sufficient to obscure the small effect of DRD4 on novelty seeking. To clarify these problems, I have reviewed the 14 replication studies from the point of view of demographic and methodological differences. It is suggested that demographic factors might be important to replicate the association between DRD4 exon III polymorphism and novelty seeking.