@misc{10481/74843,
year = {2022},
month = {3},
url = {http://hdl.handle.net/10481/74843},
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.},
organization = {European Commission	HEALTH-F2-2012-279233	
European Research Council (ERC)
European Commission	268834},
organization = {UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)	G0800270	
MR/L003120/1	
British Heart Foundation	SP/09/002	
RG/08/014	
RG13/13/30194},
organization = {National Institute for Health Research (NIHR)},
organization = {EU Sixth Framework Programme (FP6)	LSHM_CT_2006_037197},
organization = {UK Research & Innovation (UKRI)},
organization = {Medical Research Council UK (MRC)	MC_ UU_12015/1	
MC_UU_12015/5},
organization = {Danish Cancer Society},
organization = {Ligue Contre le Cancer (France)},
organization = {Institut Gustave Roussy (France)},
organization = {Mutuelle Generale de l'Education Nationale (France)},
organization = {Institut National de la Sante et de la Recherche Medicale (Inserm)},
organization = {Deutsche Krebshilfe		
Federal Ministry of Education & Research (BMBF)		
Deutsches Krebsforschungszentrum (Germany)},
organization = {Ministry of Health and Social Solidarity (Greece)		
Stavros Niarchos Foundation (Greece)		
Hellenic Health Foundation (Greece)},
organization = {Fondazione AIRC per la ricerca sul cancro		
Consiglio Nazionale delle Ricerche (CNR)		
MIUR "Dipartimenti di Eccellenza"	D15D18000410001},
organization = {Dutch Ministry of Public Health, Welfare and Sports},
organization = {LK Research Funds},
organization = {Dutch Prevention Funds		
Netherlands Organization for Scientific Research (NWO)},
organization = {World Cancer Research Fund International (WCRF)		
ERC-2009-AdG	232997},
organization = {Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway)},
organization = {Instituto de Salud Carlos III},
organization = {Junta de Andalucia},
organization = {Principality of Asturias},
organization = {Regional Government of Basque Country (Spain)		
Regional Government of Murcia (Spain)		
Regional Government of Navarra (Spain)},
organization = {Instituto de Salud Carlos III	RD06/0020},
organization = {Swedish Cancer Society		
Swedish Scientific Council (Sweden)		
Regional Government of Skane and Vasterbotten (Sweden)},
organization = {Cancer Research UK		
UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)},
organization = {Leipzig Research Center for Civilization Diseases (LIFE)},
organization = {European Commission},
organization = {Free State of Saxony},
organization = {Netherlands Heart Foundation	2013T083},
organization = {UK Research & Innovation (UKRI)},
organization = {Medical Research Council UK (MRC)	MR/P014550/1},
organization = {Sir Henry Dale Fellowship - Welcome Trust	204623/Z/16/Z},
organization = {Sir Henry Dale Fellowship - Royal Society	204623/Z/16/Z},
publisher = {Oxford University Press},
keywords = {Reproductive aging},
keywords = {Mendelian Randomization},
keywords = {Coronary heart disease},
keywords = {Risk factors},
title = {Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization},
doi = {10.1210/clinem/dgac171},
author = {Dam, Veerle and Sánchez Pérez, María José},
}