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已发表论文
东亚人群孟德尔随机化证据揭示PCOS与妊娠期糖尿病的关联
Authors Du J, Xing L, Chen Y, He Z, Zhong L, Zhao R
Received 7 August 2025
Accepted for publication 25 December 2025
Published 22 January 2026 Volume 2026:18 559022
DOI https://doi.org/10.2147/IJWH.S559022
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Jingshu Du,1,2 Liwei Xing,3 Yang Chen,4 Zhe He,5 Lanping Zhong,2 Rong Zhao1,3
1Graduate School, The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 3Postgraduate Affairs Office, The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 4Department of Gynecology, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 5Department of Acupuncture, Second Affiliated Hospital of Yunnan University Chinese Medicine, Kunming, Yunnan, People’s Republic of China
Correspondence: Rong Zhao, Graduate School, The First School of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing, Jiangsu, People’s Republic of China, Email zhaorongkm@163.com
Background: Previous Mendelian randomization (MR) studies explored causal links between polycystic ovary syndrome (PCOS) and pregnancy complications and adverse outcomes mainly in European populations, with limited generalizability. This two-sample MR study addresses this limitation.
Methods: Independent genetic instruments for PCOS were selected at genome-wide significance (P< 5× 10− 8) and statistical pruned using LDTrait. East Asian (EAS)-based genome-wide association study data were analyzed for gestational diabetes mellitus (GDM), preeclampsia, intrahepatic cholestasis of pregnancy, miscarriage, preterm birth, and gestational age at birth. The inverse variance-weighted (IVW) method with Bonferroni correction served as the primary analysis, supplemented by pleiotropy and heterogeneity tests. Multivariable MR (MVMR) assessed direct effects by adjusting for confounders.
Results: Genetically predicted PCOS was causally linked to increased GDM risk (OR=1.203, 95% CI: 1.00– 1.433), with consistent evidence across debiased IVW (OR=1.207, 95% CI: 1.008– 1.444), Bayesian Weighted MR (OR=1.204, 95% CI: 1.007– 1.440), Contamination Mixture (OR=1.231, 95% CI: 1.141– 1.526), and distortion test (OR=1.203, 95% CI: 1.120– 1.291). The strongest single nucleotide polymorphisms (SNP)-level effect was observed for rs1894116 (YAP1), followed by rs2268361 (FSHR). MVMR confirmed independence from body mass index (BMI), though the effect disappeared after adjusting for glucose and lipid traits. No causal relationships were found between PCOS and other outcomes (P> 0.05).
Conclusion: This MR study provides evidence supporting a potential causal association between genetically predicted PCOS and GDM in East Asian populations, in contrast to previous European-based findings, and highlights possible population-specific genetic differences with implications for precision risk assessment in pregnancy.
Keywords: polycystic ovary syndrome, mendelian randomization, East Asian, gestational diabetes mellitus
1Graduate School, The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 3Postgraduate Affairs Office, The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 4Department of Gynecology, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 5Department of Acupuncture, Second Affiliated Hospital of Yunnan University Chinese Medicine, Kunming, Yunnan, People’s Republic of China
Correspondence: Rong Zhao, Graduate School, The First School of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing, Jiangsu, People’s Republic of China, Email zhaorongkm@163.com
Background: Previous Mendelian randomization (MR) studies explored causal links between polycystic ovary syndrome (PCOS) and pregnancy complications and adverse outcomes mainly in European populations, with limited generalizability. This two-sample MR study addresses this limitation.
Methods: Independent genetic instruments for PCOS were selected at genome-wide significance (P< 5× 10− 8) and statistical pruned using LDTrait. East Asian (EAS)-based genome-wide association study data were analyzed for gestational diabetes mellitus (GDM), preeclampsia, intrahepatic cholestasis of pregnancy, miscarriage, preterm birth, and gestational age at birth. The inverse variance-weighted (IVW) method with Bonferroni correction served as the primary analysis, supplemented by pleiotropy and heterogeneity tests. Multivariable MR (MVMR) assessed direct effects by adjusting for confounders.
Results: Genetically predicted PCOS was causally linked to increased GDM risk (OR=1.203, 95% CI: 1.00– 1.433), with consistent evidence across debiased IVW (OR=1.207, 95% CI: 1.008– 1.444), Bayesian Weighted MR (OR=1.204, 95% CI: 1.007– 1.440), Contamination Mixture (OR=1.231, 95% CI: 1.141– 1.526), and distortion test (OR=1.203, 95% CI: 1.120– 1.291). The strongest single nucleotide polymorphisms (SNP)-level effect was observed for rs1894116 (YAP1), followed by rs2268361 (FSHR). MVMR confirmed independence from body mass index (BMI), though the effect disappeared after adjusting for glucose and lipid traits. No causal relationships were found between PCOS and other outcomes (P> 0.05).
Conclusion: This MR study provides evidence supporting a potential causal association between genetically predicted PCOS and GDM in East Asian populations, in contrast to previous European-based findings, and highlights possible population-specific genetic differences with implications for precision risk assessment in pregnancy.
Keywords: polycystic ovary syndrome, mendelian randomization, East Asian, gestational diabetes mellitus