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Genetic risk for the polycystic ovary syndrome, bone mineral density and fractures in women and men: A UK Biobank Mendelian randomisation study

Deshmukh, Harshal; Shah, Najeeb; Papageorgiou, Maria; Abdalla, Mohammed Altigani; Lhaf, Fadel; Aye, Mo; Sathyapalan, Thozhukat

Authors

Najeeb Shah

Maria Papageorgiou

Mohammed Altigani Abdalla

Fadel Lhaf

Mo Aye



Abstract

Introduction: There is conflicting data on the effect of polycystic ovary syndrome (PCOS) on bone mineral density (BMD) and fracture risk. Recent genetic data suggest that men may also carry genetic risk factors for PCOS; the associations of these factors with parameters of bone health remains unknown. We aimed to investigate if the genetic risk of PCOS is associated with BMD and fracture risk in women and men in the UK Biobank dataset. Methods: We used Mendelian randomisation (MR) analysis to test the association of genetic risk of excess testosterone in PCOS with BMD and fractures in the UK biobank study. The MR analysis was performed using linear regression analysis with the weighted genetic risk score (wGRS) as an independent variable adjusting for age, BMI and population eigenvectors. The horizontal pleiotropy in the MR analysis was tested using MR-Egger regression analysis. Results: The study consisted of 221,086 Caucasian women (mean age ± SD: 56.7 ± 7.9 years, mean body mass index [BMI] ± SD: 27.0 ± 5.1 kg/m2, mean BMD ± SD: 0.50 ± 0.11 g/cm2) and 187,816 Caucasian men (mean age ± SD: 57.1 ± 8.1 years, mean BMI ± SD: 27.7 ± 4.1 kg/m2 and mean BMD ± SD: 0.56 ± 0.12 g/cm2). Women and men self-reported 24,797 (11%) and 17,076 (10%) fractures over the last 5 years, respectively. The MR analysis showed that one SD increase in the wGRS for clinical or biochemical hyperandrogenism in PCOS was associated with significantly higher heel BMD (Beta = 0.0007 [±0.0002], P-value = 0.001) and a significantly reduced risk of fractures (OR = 0.97, P-value = 0.003) in women. A similar wGRS in men was not associated with BMD or risk of fractures. Conclusion: In this study, we showed that the excess genetic risk for hyperandrogenism in women with PCOS is associated with a higher BMD and reduced risk of fractures.

Citation

Deshmukh, H., Shah, N., Papageorgiou, M., Abdalla, M. A., Lhaf, F., Aye, M., & Sathyapalan, T. (2022). Genetic risk for the polycystic ovary syndrome, bone mineral density and fractures in women and men: A UK Biobank Mendelian randomisation study. Bone, 155, Article 116285. https://doi.org/10.1016/j.bone.2021.116285

Journal Article Type Article
Acceptance Date Dec 1, 2021
Online Publication Date Dec 10, 2021
Publication Date Feb 1, 2022
Deposit Date Dec 28, 2021
Publicly Available Date Dec 11, 2022
Journal Bone
Print ISSN 8756-3282
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 155
Article Number 116285
DOI https://doi.org/10.1016/j.bone.2021.116285
Keywords PCOS; BMD; Fractures; Genetic risk score
Public URL https://hull-repository.worktribe.com/output/3903923

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