Divergence of an association between depressive symptoms and a dopamine polygenic score in Caucasians and Asians

A recent study reported a negative association between a putatively functional dopamine (DA) polygenic score, indexing higher levels of DA signaling, and depressive symptoms. We attempted to replicate this association using data from the Duke Neurogenetics Study. Our replication attempt was made in a subsample of 520 non-Hispanic Caucasian volunteers (277 women, mean age 19.78 +/- 1.24 years). The DA polygenic score was based on the following five loci: rs27072 (SLC6A3/DAT1), rs4532 (DRD1), rs1800497 (DRD2/ANKK1), rs6280 (DRD3), and rs4680 (COMT). Because the discovery sample in the original study consisted mostly of Asian participants, we also conducted a post hoc analysis in a smaller subsample of Asian volunteers (N = 316, 179 women, mean age 19.61 +/- 1.32 years). In the primary sample of non-Hispanic Caucasians, a linear regression analysis controlling for sex, age, socioeconomic status (SES), body mass index, genetic ancestry, and both early and recent life stress, revealed that higher DA polygenic scores were associated with higher self-reported symptoms of depression. This was in contrast to the original association of higher DA polygenic scores and lower depressive symptoms. However, the direction of the association in our Asian subsample was consistent with this original finding. Our results also suggested that compared to the Asian subsample, the non-Hispanic Caucasian subsample was characterized by higher SES, lower early and recent life stress, and lower depressive symptoms. These differences may have contributed to the observed divergence in associations. Collectively, the current findings add to evidence that specific genetic associations may differ between populations and further encourage explicit modeling of race/ethnicity in examining the polygenic nature of depressive symptoms and depression.