Evidence from observational studies indicates that endometriosis and depression often co-occur. However, conflicting evidence exists, and the etiology as well as biological mechanisms underlying their comorbidity remain unknown. Utilizing genome-wide association study (GWAS) data, we comprehensively assessed the relationship between endometriosis and depression. Single nucleotide polymorphism effect concordance analysis (SECA) found a significant genetic overlap between endometriosis and depression (P_{Fsig-permuted} = 9.99 × 10⁻⁴). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (r_G = 0.27, P = 8.85 × 10⁻²⁷). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P < 5 × 10⁻⁸), of which eight are novel. Mendelian randomization analysis (MR) suggests a causal effect of depression on endometriosis. Combining gene-based association results across endometriosis and depression GWAS, we identified 22 genes with a genome-wide significant Fisher’s combined P value (FCP_gene < 2.75 × 10⁻⁶). Genes with a nominal gene-based association (P_gene < 0.05) were significantly enriched across endometriosis and depression (P_{binomial-test} = 2.90 × 10⁻⁴). Also, genes overlapping the two traits at P_gene < 0.1 (P_{binomial-test} = 1.31 × 10⁻⁵) were significantly enriched for the biological pathways ‘cell–cell adhesion’, ‘inositol phosphate metabolism’, ‘Hippo-Merlin signaling dysregulation’ and ‘gastric mucosa abnormality’. These results reveal a shared genetic etiology for endometriosis and depression. Indeed, additional analyses found evidence of a causal association between each of endometriosis and depression and at least one abnormal condition of gastric mucosa. Our study confirms the comorbidity of endometriosis and depression, implicates links with gastric mucosa abnormalities in their causal pathways and reveals potential therapeutic targets for further investigation.

观察性研究的证据表明，子宫内膜异位症和抑郁症经常同时发生。然而，存在相互矛盾的证据，其共病的病因和生物学机制仍然未知。利用全基因组关联研究（GWAS）数据，我们全面评估了子宫内膜异位症与抑郁症之间的关系。单核苷酸多态性效应一致性分析 (SECA) 发现子宫内膜异位症和抑郁症之间存在显着的遗传重叠 ( P _{Fsig - permuted}  = 9.99 × 10 ^-4 )。连锁不平衡评分回归 (LDSC) 分析估计两个性状之间存在正且高度显着的遗传相关性 ( r _G  = 0.27, P = 8.85 × 10 ^-27 )。子宫内膜异位症和抑郁症 GWAS 的荟萃分析（样本量 = 709,111）确定了 20 个独立的全基因组显着位点（P  < 5 × 10 ^-8），其中 8 个是新的。孟德尔随机化分析 (MR) 表明抑郁症对子宫内膜异位症存在因果关系。结合跨子宫内膜异位症和抑郁症 GWAS 的基于基因的关联结果，我们确定了 22 个具有全基因组显着 Fisher 组合P值的基因（FCP_基因 < 2.75 × 10 ^-6）。具有名义基因关联的基因（P_基因 < 0.05）在子宫内膜异位症和抑郁症中显着富集（P_{二项式-测试} = 2.90 × 10 ^-4 )。此外，在P_基因 < 0.1 ( P_{二项式-检验} = 1.31 × 10 ^-5) 显着富集了“细胞-细胞粘附”、“肌醇磷酸代谢”、“Hippo-Merlin 信号传导失调”和“胃黏膜异常”的生物学途径。这些结果揭示了子宫内膜异位症和抑郁症的共同遗传病因。事实上，额外的分析发现了子宫内膜异位症和抑郁症与至少一种胃粘膜异常状况之间存在因果关系的证据。我们的研究证实了子宫内膜异位症和抑郁症的共病，在其因果通路中与胃粘膜异常有关，并揭示了潜在的治疗靶点以供进一步研究。