Department of Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Regional Alliance for Promoting Liaison Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Psychiatry Clin Neurosci. 2024 Nov;78(11):712-720. doi: 10.1111/pcn.13731. Epub 2024 Sep 17.
Genome-wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD-associated loci.
The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders.
A meta-analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. 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.
The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis.
基于具有多种族背景的累积队列的产后抑郁症（PPD）全基因组关联研究（GWAS）未能确定显著相关的基因座。在此，我们对日本围产期妇女进行了 GWAS 研究，并结合详细的混杂信息，以发现与 PPD 相关的基因座。
第一和第二队列（在东北医科大学 Mega 银行项目中招募的 9260 和 8582 名围产期女性）和第三队列（在名古屋大学招募的 997 名）进行了基因分型。其中，1421、1264 和 225 名女性在分娩后 1 个月根据爱丁堡产后抑郁量表被诊断为 PPD。选择对 PPD 遗传易感性影响最大的混杂因素，并进行逻辑回归分析，以评估在调整混杂因素后与 PPD 的遗传关联。
通过将分娩次数和共同居住的家庭成员数量作为最有影响的混杂因素纳入分析，三个队列的 GWAS 结果的荟萃分析确定了 PPD 与以下基因座之间的显著关联（P < 5 × 10）：DAB1 上的 rs377546683、UGT8 附近的 rs11940752、rs141172317、rs117928019、rs76631412、rs118131805、DOCK2 上的 rs188907279、ZNF572 附近的 rs188907279、rs504378、rs690150、rs491868、rs689917、rs474978、rs690118、rs690253 附近的 DIRAS2、ZNF618 上的 rs1435984417、PTPRM 附近的 rs57705782 和 PDGFB 附近的 rs185293917。途径分析表明，与 PPD 提示相关的 SNPs 主要在包括长期抑郁、GnRH 信号、谷氨酸能突触、催产素信号和 Rap1 信号在内的类别中过表达。
本 GWAS 研究确定了与 PPD 显著相关的 8 个基因座，这可能阐明了其发病机制的遗传结构。
