A bidirectional 2-sample Mendelian randomization study of depressed mood and premature ovarian insufficiency

This study aimed to investigate the bidirectional causal relationship between depressed mood and premature ovarian insufficiency (POI) using a Mendelian randomization (MR) method. Genome wide association study data on depressed mood and POI were obtained using the IEU Open genome wide association study website. Closely related and independent single nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs) from depressed mood according to preset thresholds, and the association between depressed mood and the risk of developing POI was mainly assessed using inverse-variance weighted (IVW); the heterogeneity of SNPs was also assessed using CochranQ test. The MR-PRESSO test was used to detect the presence of outlier SNPs, and the MR-Egger intercept test was used to test the horizontal pleiotropy of SNPs. A "leave-one-out" sensitivity analysis was performed to test whether the MR results were influenced by a single SNP, and a 2-way MR analysis was performed by interchanging the screening processes for depressed mood and POI. The results of MR analysis indicated that there was no causal relationship between depressed mood and the occurrence of POI (odds ratio = 0.601, 95% confidence interval: 0.105-3.430, P = .566), and in the reverse MR analysis, there was no significant causal relationship between POI and depressed mood (odds ratio = 0.999, 95% confidence interval: 0.996-1.003, P = .663), none of the instrumental variables in the bidirectional MR analysis showed horizontal pleiotropy and heterogeneity. Genetics-based MR analysis found no significant causal relationship between depressed mood and POI.