Bidirectional Mendelian Randomization Analysis of Mood Disorders and Risk of Preeclampsia-Eclampsia

Chenyang Zhao,1,2,* Fangjun Chen,3,* Qiong Li,1,2 Lixiu Peng,1 Chaoyan Yue4 1Department of Obstetrics and Gynecology, The First People’s Hospital of Chenzhou, Chenzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, Jinan University, Guangzhou, People’s Republic of China; 3Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoyan Yue, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fang Xie Road, No. 419, Shanghai, People’s Republic of China, Email [email protected]: Mood disorders and preeclampsia-eclampsia (PE) are two major public health problems. The genetic association of the two problems is unclear. We conducted a bidirectional Mendelian randomization (MR) analysis to explore the potential casual relationships between mood disorder subtypes (bipolar disorder, depression, manic/hyper symptoms) and PE.Methods: Summary statistics for bipolar disorder (7481 cases and 9250 controls), depression (13,559 cases and 435,855 controls), manic/hyper symptoms (3177 cases and 28,140 controls) were derived from IEU open GWAS project. Summary data for PE were obtained from FinnGen consortium (7965 cases and 211,852 controls) and IEU open GWAS project (2355 cases and 264,887 controls). Four methods were applied in our MR analysis, including the inverse variance weighting (IVW), MR-Egger, weighted median and weighted mode. Meta-analysis method was used to assess the combined effect from two independent database. A series of sensitivity analyses were conducted to estimate the robustness of results.Results: The combined effect from two data sources indicated that there were casual associations between bipolar disorder and PE (OR = 1.15, 95% CI: 1.08– 1.22, P < 0.001), depression and PE (OR = 1.07, 95% CI: 1.01– 1.13, P = 0.01). No significant association was observed between manic/hyper symptoms and PE. Reverse MR analysis demonstrated no casual effect of PE on bipolar disorder, depression or manic/hyper symptoms. Sensitivity analysis confirmed the robustness of the bidirectional MR results.Conclusion: Our findings provided evidence that bipolar disorder and depression are causally associated with PE.Keywords: mood disorder, preeclampsia-eclampsia, Mendelian randomization analysis