Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study

Background: Observational studies have reported that individuals diagnosed with polycystic ovary syndrome (PCOS) face a heightened vulnerability to developing post-traumatic stress disorder (PTSD). However, it is unclear whether this relationship is causal. Consequently, we implemented a bidirection...

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Main Authors: Xian Zhang, Jie Song, Bin Liu, Minchen Dai, Binxiang Wang, Xiaowei Cai, Yifan Hu, Yingying Mao, Fan Qu
Format: Article
Language:English
Published: IMR Press 2023-09-01
Series:Clinical and Experimental Obstetrics & Gynecology
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Online Access:https://www.imrpress.com/journal/CEOG/50/9/10.31083/j.ceog5009193
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author Xian Zhang
Jie Song
Bin Liu
Minchen Dai
Binxiang Wang
Xiaowei Cai
Yifan Hu
Yingying Mao
Fan Qu
author_facet Xian Zhang
Jie Song
Bin Liu
Minchen Dai
Binxiang Wang
Xiaowei Cai
Yifan Hu
Yingying Mao
Fan Qu
author_sort Xian Zhang
collection DOAJ
description Background: Observational studies have reported that individuals diagnosed with polycystic ovary syndrome (PCOS) face a heightened vulnerability to developing post-traumatic stress disorder (PTSD). However, it is unclear whether this relationship is causal. Consequently, we implemented a bidirectional Mendelian randomization (MR) analysis to examine the empirical causal association of PCOS and PTSD. Methods: We acquired genetic association data for PCOS through a comprehensive meta-analysis from several large-scale genome-wide association studies (GWASs), which enrolled 10,074 cases and 103,164 controls. For PTSD, we obtained data from a GWAS performed by the Psychiatric Genomics Consortium Posttraumatic Stress Disorder (PGC-PTSD) group. The study included a total of 23,212 cases of PTSD and 151,447 controls of European ancestry. For both PCOS and PTSD, we carefully selected genetic instruments that met the rigorous significance threshold (p < 5 × 10-8, r2 < 0.01). To investigate the causal association between PCOS and PTSD, we conducted bidirectional Mendelian randomization (MR) analyses. The primary analysis employed the inverse-variance weighted (IVW) method, complemented by alternative MR approaches such as the maximum-likelihood method, MR-Egger regression, Mendelian randomization-Robust Adjusted Profile Score (MR-RAPS), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Sensitivity analyses were also carried out to verify the robustness of this association. Results: In this study, we identified and utilized 14 genetic variants as instruments for PCOS, while 2 genetic variants were selected as instruments for PTSD. Our findings demonstrated that a genetic predisposition to PCOS was significantly associated with an elevated risk of developing PTSD (odds ratio (OR) = 1.11, 95% confidence interval (CI): 1.03–1.19, p = 7.27 × 10-3 for IVW). MR-Egger regression analysis was performed, and the results did not provide evidence of directional pleiotropy (p intercept = 0.187). Sensitivity analyses utilizing alternative MR methods consistently yielded similar results, supporting the robustness of our findings. Furthermore, in the reverse MR analysis, we observed no significant association between genetic predisposition to PTSD and the risk of developing PCOS (OR = 1.15, 95% CI: 0.69–1.91, p = 0.586 for IVW). Comparable null associations were also observed when alternative MR methods were employed. Conclusions: Through a genetic epidemiological approach, we found that genetic predisposition to PCOS was associated with an increased risk of PTSD, suggesting a potential causal relationship between PCOS and PTSD. Nonetheless, further investigation is necessary to elucidate the underlying mechanism through which PCOS contributes to the development of PTSD.
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spelling doaj-art-6a8f384a0f3b4a818235ecaec79ab2802025-08-20T01:57:15ZengIMR PressClinical and Experimental Obstetrics & Gynecology0390-66632023-09-0150919310.31083/j.ceog5009193S0390-6663(23)02129-2Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization StudyXian Zhang0Jie Song1Bin Liu2Minchen Dai3Binxiang Wang4Xiaowei Cai5Yifan Hu6Yingying Mao7Fan Qu8Department of Chinese Integrative Medicine, Women’s Hospital, School of Medicine, Zhejiang University, 310006 Hangzhou, Zhejiang, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, ChinaDepartment of Chinese Integrative Medicine, Women’s Hospital, School of Medicine, Zhejiang University, 310006 Hangzhou, Zhejiang, ChinaDepartment of Chinese Medicine, Xinchang People’s Hospital, 312500 Shaoxing, Zhejiang, ChinaDepartment of Chinese Medicine, Xinchang People’s Hospital, 312500 Shaoxing, Zhejiang, ChinaThe Fourth Affiliated Hospital, School of Medicine, Zhejiang University, 322000 Yiwu, Zhejiang, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, ChinaDepartment of Chinese Integrative Medicine, Women’s Hospital, School of Medicine, Zhejiang University, 310006 Hangzhou, Zhejiang, ChinaBackground: Observational studies have reported that individuals diagnosed with polycystic ovary syndrome (PCOS) face a heightened vulnerability to developing post-traumatic stress disorder (PTSD). However, it is unclear whether this relationship is causal. Consequently, we implemented a bidirectional Mendelian randomization (MR) analysis to examine the empirical causal association of PCOS and PTSD. Methods: We acquired genetic association data for PCOS through a comprehensive meta-analysis from several large-scale genome-wide association studies (GWASs), which enrolled 10,074 cases and 103,164 controls. For PTSD, we obtained data from a GWAS performed by the Psychiatric Genomics Consortium Posttraumatic Stress Disorder (PGC-PTSD) group. The study included a total of 23,212 cases of PTSD and 151,447 controls of European ancestry. For both PCOS and PTSD, we carefully selected genetic instruments that met the rigorous significance threshold (p < 5 × 10-8, r2 < 0.01). To investigate the causal association between PCOS and PTSD, we conducted bidirectional Mendelian randomization (MR) analyses. The primary analysis employed the inverse-variance weighted (IVW) method, complemented by alternative MR approaches such as the maximum-likelihood method, MR-Egger regression, Mendelian randomization-Robust Adjusted Profile Score (MR-RAPS), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Sensitivity analyses were also carried out to verify the robustness of this association. Results: In this study, we identified and utilized 14 genetic variants as instruments for PCOS, while 2 genetic variants were selected as instruments for PTSD. Our findings demonstrated that a genetic predisposition to PCOS was significantly associated with an elevated risk of developing PTSD (odds ratio (OR) = 1.11, 95% confidence interval (CI): 1.03–1.19, p = 7.27 × 10-3 for IVW). MR-Egger regression analysis was performed, and the results did not provide evidence of directional pleiotropy (p intercept = 0.187). Sensitivity analyses utilizing alternative MR methods consistently yielded similar results, supporting the robustness of our findings. Furthermore, in the reverse MR analysis, we observed no significant association between genetic predisposition to PTSD and the risk of developing PCOS (OR = 1.15, 95% CI: 0.69–1.91, p = 0.586 for IVW). Comparable null associations were also observed when alternative MR methods were employed. Conclusions: Through a genetic epidemiological approach, we found that genetic predisposition to PCOS was associated with an increased risk of PTSD, suggesting a potential causal relationship between PCOS and PTSD. Nonetheless, further investigation is necessary to elucidate the underlying mechanism through which PCOS contributes to the development of PTSD.https://www.imrpress.com/journal/CEOG/50/9/10.31083/j.ceog5009193genetic instrumentsmendelian randomizationpolycystic ovary syndromepost-traumatic stress disorder
spellingShingle Xian Zhang
Jie Song
Bin Liu
Minchen Dai
Binxiang Wang
Xiaowei Cai
Yifan Hu
Yingying Mao
Fan Qu
Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
Clinical and Experimental Obstetrics & Gynecology
genetic instruments
mendelian randomization
polycystic ovary syndrome
post-traumatic stress disorder
title Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
title_full Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
title_fullStr Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
title_full_unstemmed Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
title_short Assessing the Potential Causal Relationship between Polycystic Ovary Syndrome and Post-Traumatic Stress Disorder: A Bidirectional Mendelian Randomization Study
title_sort assessing the potential causal relationship between polycystic ovary syndrome and post traumatic stress disorder a bidirectional mendelian randomization study
topic genetic instruments
mendelian randomization
polycystic ovary syndrome
post-traumatic stress disorder
url https://www.imrpress.com/journal/CEOG/50/9/10.31083/j.ceog5009193
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