Loci Associated with Postpartum Depression: A Genome-Wide Association Study

Abstract

Abstract Although postpartum depression (PPD) has been identified as a severe public health problem, its genetic basis has yet to be elucidated. Therefore, we conducted a genome-wide association study (GWAS) to identify the loci significantly associated with PPD. The first and second cohorts (n = 9,260 and n = 8,582 perinatal women enrolled in the Tohoku Medical Megabank Project [TMM]), and the third cohort (n = 997), recruited at Nagoya University, were subjected to genotyping. PPD was defined based on the Edinburgh Postnatal Depression Scale one month after delivery. Logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for the most influential confounders, including the number of deliveries and the number of family members living together. A meta-analysis of GWAS results from the three cohorts indicated the following loci as significantly associated with PPD (P < 5´10–8): rs377546683 at DAB1 (1p32.2), rs11940752 near UGT8 (4q26), rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2 (5q35.1), rs188907279 near ZNF572 (8q24.13), rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2 (9q22.2), rs1435984417 at ZNF618 (9q31.3), rs57705782 near PTPRM (18p11.23), and rs185293917 near PDGFB (22q13.1). Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over-represented in categories including long-term depression, GnRH signaling, Glutamatergic synapse, Oxytocin signaling, and Rap1 signaling. Thus, the current GWAS study identified eight loci significantly associated with PPD, which may enlighten the genetic structure underlying the pathogenesis of PPD.