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ORIGINAL RESEARCH article
Front. Genet.
Sec. Applied Genetic Epidemiology
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1393106
This article is part of the Research Topic Advancements and Prospects of Genome-wide Association Studies View all 5 articles
Causal Relationship Between Reproductive Factors and Female Bone Density: A Univariate and Multivariate Mendelian Randomization Study
Provisionally accepted- 1 Guangdong Medical University, Zhanjiang, Guangdong, China
- 2 Yuebei People's Hospital, Shaoguan, China
Objective: Observational studies have found associations between reproductive factors and bone density in women. However, the causal relationships are not well understood. This study aims to investigate whether various reproductive factors are causally related to bone density at different skeletal sites using both univariable and multivariable Mendelian randomization(MR)methods.Methods: The study incorporated four reproductive factors, namely age at menarche (AAM), age at first live birth (AFB), age at menopause (ANM), and age at last live birth (ALB), as well as five distinct skeletal sites, including bone mineral density (BMD), heel calcaneus BMD, ultradistal forearm bone mineral density (FA-BMD), lumbar spine bone mineral density (LS-BMD), and femoral neck bone mineral density (FN-BMD). Univariable two-sample MR and multivariable MR analyses were conducted using data from published genome-wide association studies (GWASs). A total of 150 single nucleotide polymorphisms (SNPs) associated with the four reproductive factors were extracted from GWAS databases. The primary statistical analysis method utilized in this study was the inverse variance-weighted (IVW) method.Results: In the univariate MR analysis, we observed causal connections between four reproductive factors and bone density. Specifically, AAM had a significant impact on BMD and heel calcaneus BMD. Age at first live birth was negatively associated with FA-BMD. Age at last live birth showed a negative correlation with BMD and heel calcaneus BMD. ANM exhibited positive associations with BMD, heel calcaneus BMD, FA-BMD, and LS-BMD. Subsequently, we performed a multivariable MR analysis to examine the combined effects of multiple variables, which confirmed the persistence of associations between age at menopause and bone density at various sites. Additionally, we found a negative correlation between age at last live birth and heel calcaneus BMD.This study offers a fresh perspective on the prevention of osteoporosis in women, explicitly stating that reproductive factors such as early menopause and late childbirth play a significant predictive role in individual bone density decline. Therefore, when developing osteoporosis screening and management protocols, reproductive factors should be included for a more comprehensive guidance of clinical practice.
Keywords: Reproductive factors, Mendelian randomization, BMD, Osteoporosis, female
Received: 28 Feb 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Lin, Zuo, Hu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hongbo Hu, Yuebei People's Hospital, Shaoguan, 512025, China
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