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No association effect of genetic polymorphism was observed between polycystic ovary syndrome and cardiovascular diseases risk: a mendelian randomization study

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Abstract

Objective

Polycystic ovary syndrome (PCOS) is one of the risk factors for cardiovascular diseases (CVDs). However, the possible association between PCOS and common CVDs remains inconclusive. The aim of this study was to explore the potential relationship between PCOS and CVDs using genetic polymorphisms.

Methods

We conducted two-sample Mendelian randomization (MR) analyses. In our study, 14 single nucleotide polymorphisms (SNPs) in Europeans and another 13 SNPs in Asians were applied as instrumental variables for PCOS. The largest published meta-genome-wide association studies of European ancestry and the BioBank Japan Project of Asian ancestry were used to collect the outcome data. MR analysis was performed using inverse variance weighting as the primary method. Several sensitivity analyses and instrumental variable strength evaluations were also performed to verify the reliability of results.

Results

Our analysis revealed that any potential causal association between genetically-predicted PCOS and the risk of CVDs do not exist. These CVDs include peripheral artery disease, atrial fibrillation, arrhythmia, cardiovascular diseases, heart failure, peripheral vascular disease, hypertension, ischemic stroke, myocardial infarction and venous thromboembolisms. Associations could not be found even after the SNPs linked to these possible confounders (body mass index, waist-to-hip ratio, and serum testosterone) were deleted. Sensitivity analysis demonstrated no presence of horizontal pleiotropy or heterogeneity.

Conclusion

The present mendelian randomization study suggests that genetically-predicted PCOS may not be associated with the risk of CVDs.

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Data availability

Publicly available data were analyzed in this study, which can be found here: https://www.ebi.ac.uk/gwas/, https://gwas.mrcieu.ac.uk/datasets/. The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

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Acknowledgements

The authors acknowledge all GWAS participants and investigators for their contribution to the summary statistic data. The authors thank all investigators for sharing these data.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Beijing, China

    Xiao Zhang & Shaowei Wang

  2. Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China

    Xiao Zhang & Shaowei Wang

  3. Graduate School of Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Xiao Zhang & Shaowei Wang

  4. Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China

    Zhao Huangfu

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  1. Xiao Zhang
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  2. Zhao Huangfu
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  3. Shaowei Wang
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Contributions

All authors contributed to the study conception and design. XZ and ZH conducted data acquisition and performed data analysis. XZ and SW performed manuscript revision. Informed consent was obtained from all individual participants included in the study.

Corresponding author

Correspondence to Shaowei Wang.

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Zhang, X., Huangfu, Z. & Wang, S. No association effect of genetic polymorphism was observed between polycystic ovary syndrome and cardiovascular diseases risk: a mendelian randomization study. Endocrine 82, 695–706 (2023). https://doi.org/10.1007/s12020-023-03467-8

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  • DOI: https://doi.org/10.1007/s12020-023-03467-8

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