Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.
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Authors
Peters, Sanne AE
Tikk, Kaja
Oliver-Williams, Clare
Wood, Angela M
Tjønneland, Anne
Dahm, Christina C
Schulze, Matthias B
Tumino, Rosario
Matullo, Giuseppe
Boer, Jolanda MA
Verschuren, WM Monique
Waaseth, Marit
Pérez, Maria José Sánchez
Amiano, Pilar
Imaz, Liher
Moreno-Iribas, Conchi
Melander, Olle
Nordendahl, Maria
Wennberg, Patrik
Key, Timothy J
Santiuste, Carmen
Kaaks, Rudolf
Langenberg, Claudia
Wareham, Nicholas J
Erdmann, Jeanette
Willenborg, Christina
Delgado, Graciela
März, Winfried
Kanoni, Stavroula
Dedoussis, George
Teren, Andrej
Butterworth, Adam S
van der Schouw, Yvonne T
Publication Date
2022-06-16Journal Title
J Clin Endocrinol Metab
ISSN
0021-972X
Publisher
The Endocrine Society
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Dam, V., Onland-Moret, N. C., Burgess, S., Chirlaque, M., Peters, S. A., Schuit, E., Tikk, K., et al. (2022). Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.. J Clin Endocrinol Metab https://doi.org/10.1210/clinem/dgac171
Abstract
BACKGROUND: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. OBJECTIVES: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. DESIGN: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. PARTICIPANTS: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. MAIN OUTCOME MEASURES: CHD, CHD risk factors, and ANM. RESULTS: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. CONCLUSION: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.
Keywords
Mendelian Randomization, Reproductive aging, coronary heart disease, risk factors
Sponsorship
MRC (MC_UU_00006/1)
Medical Research Council (G0800270)
European Research Council (268834)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_UU_12015/5)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
Embargo Lift Date
2023-03-20
Identifiers
External DOI: https://doi.org/10.1210/clinem/dgac171
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336942
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