Objective:

Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.

Method:

Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.

Results:

No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.

Conclusions:

While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

中文翻译：

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产后抑郁症全基因组关联研究的荟萃分析

客观的：

产后抑郁症 (PPD) 是重度抑郁症 (MDD) 的一种常见亚型，遗传性更强，但在精神遗传学方面尚未得到充分研究。作者对全基因组关联研究 (GWAS) 进行了荟萃分析，以研究 PPD 的遗传结构。

方法：

对 18 个欧洲血统队列（17,339 例 PPD 病例和 53,426 名对照）、一组东亚血统（975 例病例和 3,780 名对照）和一组非洲血统（456 例病例和 1,255 名对照）进行荟萃分析，总计 18,770 名PPD 病例和 58,461 例对照。GWAS 后分析包括 1) 基于单核苷酸多态性 (SNP) 的遗传力（），2）PPD 与其他表型之间的遗传相关性，以及 3）PPD GWAS 结果在 27 种人体组织和来自小鼠中枢和周围神经系统的 265 种细胞类型中的富集。

结果：

在欧洲或跨祖先荟萃分析中，没有任何 SNP 具有全基因组显着性。这PPD 为 0.14（SE=0.02）。估计 PPD 与 MDD、双相情感障碍、焦虑症、创伤后应激障碍、失眠、初潮年龄和多囊卵巢综合征之间存在显着的遗传相关性。细胞类型富集分析表明，丘脑中存在抑制性神经元，下丘脑间隔核中存在胆碱能神经元，这种模式与 MDD 不同。

结论：

虽然需要更多样本才能达到全基因组的显着性水平，但所提供的结果证实 PPD 是一种多基因和可遗传的表型。还有证据表明，尽管 PPD 与 MDD 高度相关，但 PPD 可能具有独特的遗传成分。细胞富集结果表明 GABA 能神经元与美国食品和药物管理局批准的唯一治疗 PPD 的药物（brexanolone）具有共同的机制。