Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization
Dam, V. ; Melander, O. LU
and Van Der Schouw, Y.T.
(2022)
In Journal of Clinical Endocrinology and Metabolism
107(7).
p.2952-2961
- 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... (More)
- 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. © 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. (Less)
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- author
- Dam, V.
; Melander, O.
LU
and Van Der Schouw, Y.T.
- author collaboration
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- coronary heart disease, Mendelian Randomization, reproductive aging, risk factors, aging, coronary artery disease, female, genetics, genome-wide association study, human, male, Mendelian randomization analysis, procedures, single nucleotide polymorphism, Aging, Coronary Disease, Female, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 107
- issue
- 7
- pages
- 2952 - 2961
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85132454263
- pmid:35306566
- ISSN
- 0021-972X
- DOI
- 10.1210/clinem/dgac171
- language
- English
- LU publication?
- yes
- id
- e3d18d3f-9f96-46cb-92e9-2cfaf4c14900
- date added to LUP
- 2022-09-14 13:30:55
- date last changed
- 2024-01-18 14:31:17
@article{e3d18d3f-9f96-46cb-92e9-2cfaf4c14900,
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. © 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.}},
author = {{Dam, V. and Melander, O. and Van Der Schouw, Y.T.}},
issn = {{0021-972X}},
keywords = {{coronary heart disease; Mendelian Randomization; reproductive aging; risk factors; aging; coronary artery disease; female; genetics; genome-wide association study; human; male; Mendelian randomization analysis; procedures; single nucleotide polymorphism; Aging; Coronary Disease; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide}},
language = {{eng}},
number = {{7}},
pages = {{2952--2961}},
publisher = {{Oxford University Press}},
series = {{Journal of Clinical Endocrinology and Metabolism}},
title = {{Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization}},
url = {{http://dx.doi.org/10.1210/clinem/dgac171}},
doi = {{10.1210/clinem/dgac171}},
volume = {{107}},
year = {{2022}},
}