Causal relationships of anxiety, depression and neuroticism with recurrent spontaneous abortion: a Mendelian randomization analysis

To explore the causal relationships of anxiety, depression and neuroticism with recurrent spontaneous abortion（RSA）.

Genome-wide association study（GWAS） data were used to extract single nucleotide polymorphisms（SNPs） closely related to anxiety, depression and neuroticism as instrumental variables（IVs）. Inverse variance weighting（IVW）, weighted median estimator（WME）, weighted mode（WM） and Mendelian randomization（MR）-Egger regression were employed for MR analysis to evaluate the causal effects of anxiety, depression and neuroticism with RSA, and to analyze heterogeneity, gene pleiotropy and sensitivity.

A total of 46 SNPs were extracted from GWAS data as IVs（5 anxiety SNPs, 9 depression SNPs, and 32 neuroticism SNPs）. IVW, WME, WM and MR-Egger regression analysis revealed that the odds ratio（OR） and 95% confidence interval（CI） of anxiety data were 1. 07（0. 86-1. 32）, 1. 10（ 0. 85-1. 43）, 1. 14（0. 81-1. 59） and 1. 18（0. 53-2. 61）; those of depression data were 1. 11（0. 93-1. 32）, 1. 05（0. 83-1. 32）, 0. 96（0. 67-1. 38） and 0. 57（0. 25-1. 31）; those of neuroticism data were 1. 01（0. 75-1. 36）, 1. 07（0. 73-1. 56）, 1. 02（0. 49-2. 12） and 2. 40（0. 46-12. 44）, but none of the above causal analyses were statistically significant（all P＞0. 05）. After reliability analysis, the Cochran’s Q test for heterogeneity evaluation was not significant（P＞0. 05）, the MR-Egger regression intercepts for gene pleiotropy evaluation were all close to 0（P＞0. 05）, and the sensitivity evaluation "Leave-one-out" test also shows that the combined causal effect values are similar.

There dose not exist causal relationships of anxiety, depression and neuroticism with RSA. The reliability test shows that the results are relatively robust.