Research Paper Volume 13, Issue 15 pp 19722—19749
The role of age at menarche and age at menopause in Alzheimer’s disease: evidence from a bidirectional mendelian randomization study
- 1 Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, China
- 2 Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning 530021, Guangxi, China
- 3 Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning 530021, Guangxi, China
- 4 Guangxi Key Laboratory of Colleges and Universities, Nanning 530021, Guangxi, China
- 5 School of Public Health of Guangxi Medical University, Nanning 530021, Guangxi, China
- 6 Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
Received: December 27, 2020 Accepted: May 31, 2021 Published: August 4, 2021
https://doi.org/10.18632/aging.203384How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The association between endogenous estrogen exposure and Alzheimer’s disease (AD) remains inconclusive in previous observational studies, and few Mendelian randomization (MR) studies have focused on their causality thus far. We performed a bidirectional MR study to clarify the causality and causal direction of age at menarche and age at menopause, which are indicators of endogenous estrogen exposure, on AD risk. We obtained all genetic datasets for the MR analyses using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. The MR analyses indicated no significant causal relationship between the genetically determined age at menarche (outlier-adjusted inverse variance weighted odds ratio [IVWOR] = 0.926; 95% confidence interval [CI], 0.803-1.066) or age at menopause (outlier-adjusted IVWOR = 0.981; 95% CI, 0.941-1.022) and AD risk. Similarly, AD did not show any causal association with age at menarche or age at menopause. The sensitivity analyses yielded similar results. In contrast, an inverse association was detected between age at menarche and body mass index (BMI, outlier-adjusted IVW β = -0.043; 95% CI, -0.077 to -0.009). Our bidirectional MR study provides no evidence for a causal relationship between the genetically determined age at menarche or age at menopause and AD susceptibility, or vice versa. However, earlier menarche might be associated with higher adult BMI.