Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.

Aging / genetics Coronary Disease / epidemiology Female Genome-Wide Association Study / methods Humans Male Mendelian Randomization Analysis Polymorphism, Single Nucleotide
Mendelian Randomization coronary heart disease reproductive aging risk factors

Journal

The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362

Informations de publication

Date de publication:
16 06 2022
Historique:
received: 22 05 2021
pubmed: 21 3 2022
medline: 22 6 2022
entrez: 20 3 2022
Statut: ppublish

Résumé

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. 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. 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. Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. CHD, CHD risk factors, and ANM. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1210/clinem/dgac171 PMID: 35306566 PMC: PMC9202700
pubmed: 35306566
pii: 6550950
doi: 10.1210/clinem/dgac171
pmc: PMC9202700
mid: EMS144700
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2952-e2961

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P014550/1
Pays : United Kingdom
Organisme : European Union Framework 7
ID : HEALTH-F2-2012-279233
Organisme : British Heart Foundation
ID : SP/09/002
Pays : United Kingdom
Organisme : European Research Council
ID : 268834
Pays : International
Organisme : Medical Research Council
ID : RG13/13/30194
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/08/014
Pays : United Kingdom
Organisme : Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC
ID : RD06/0020
Organisme : Medical Research Council Epidemiology Unit
ID : MC_UU_12015/1
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : UK Medical Research Council Skills Development Fellowship
ID : MR/P014550/1
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : Sixth Framework Programme
ID : LSHM_CT_2006_037197
Organisme : National Institute for Health Research
Organisme : World Cancer Research Fund
ID : ERC-2009-AdG 232997
Organisme : Medical Research Council
ID : G0800270
Pays : United Kingdom
Organisme : Royal Society
ID : 204623/Z/16/Z
Organisme : Dutch Heart Foundation
ID : 2013T083

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

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Auteurs

Veerle Dam (V)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.
Netherlands Heart Institute, DG 3501 Utrecht, the Netherlands.
ORCID: 0000-0002-5982-232X

N Charlotte Onland-Moret (NC)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.
ORCID: 0000-0002-2360-913X

Stephen Burgess (S)

MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK.
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Homerton College, Cambridge, UK.
ORCID: 0000-0001-5365-8760

Maria-Dolores Chirlaque (MD)

Department of Epidemiology, Regional Health Authority, IMIB-Arrixaca, Murcia University, 30001 Murcia, Spain.
Department of Public Health and Clinical Medicine, Umea University, 901 87 Umea, Sweden.
ORCID: 0000-0001-9242-3040

Sanne A E Peters (SAE)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.
The George Institute for Global Health, Imperial College London, London W12 0BZ, UK.

Ewoud Schuit (E)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.
ORCID: 0000-0002-9548-3214

Kaja Tikk (K)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
German Cancer Consortium, DKFZ, 69120 Heidelberg, Germany.

Elisabete Weiderpass (E)

International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France.
ORCID: 0000-0003-2237-0128

Clare Oliver-Williams (C)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Homerton College, Cambridge, UK.

Angela M Wood (AM)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Anne Tjønneland (A)

Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Christina C Dahm (CC)

Department of Public Health, Aarhus University, 8000 Aarhus, Denmark.

Kim Overvad (K)

Department of Public Health, Aarhus University, 8000 Aarhus, Denmark.
Department of Cardiology, Aalborg University Hospital, 9000 Aalborg, Denmark.
ORCID: 0000-0001-6429-7921

Marie-Christine Boutron-Ruault (MC)

INSERM, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones, and Women's Health Team, Institut Gustave Roussy, 94 805 Villejuif, France.
ORCID: 0000-0002-5956-5693

Matthias B Schulze (MB)

Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany.

Antonia Trichopoulou (A)

Hellenic Health Foundation, 115 27 Athens, Greece.
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens 115 27, Greece.
ORCID: 0000-0002-7204-6396

Pietro Ferrari (P)

International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France.
ORCID: 0000-0001-9358-7338

Giovanna Masala (G)

Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, 50139 Florence, Italy.
ORCID: 0000-0002-5758-9069

Vittorio Krogh (V)

Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
ORCID: 0000-0003-0122-8624

Rosario Tumino (R)

Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" hospital, ASP Ragusa, 97100 Ragusa, Italy.

Giuseppe Matullo (G)

Department of Medical Sciences, University of Torino, 10124 Torino, Italy.
Italian Institute for Genomic Medicine-IIGM/HuGeF, 10126 Torino, Italy.

Salvatore Panico (S)

Dipartimento di medicina clinica e chirurgia, Federico II University, 80126 Naples, Italy.
ORCID: 0000-0002-5498-8312

Jolanda M A Boer (JMA)

National Institute for Public Health and the Environment, 3720 BA Bilthoven, the Netherlands.

W M Monique Verschuren (WMM)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.
National Institute for Public Health and the Environment, 3720 BA Bilthoven, the Netherlands.

Marit Waaseth (M)

Department of Pharmacy, Faculty of Health Sciences, UiT the Arctic University of Norway, N-9037 Tromsø, Norway.

Maria José Sánchez Pérez (MJS)

Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, 18011 Granada, Spain.
CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.

Pilar Amiano (P)

CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
Public Health Division of Gipuzkoa, Biodonostia Research Institute, 20014 San Sebastian, Spain.

Liher Imaz (L)

CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
Public Health Division of Gipuzkoa, Biodonostia Research Institute, 20014 San Sebastian, Spain.

Conchi Moreno-Iribas (C)

Instituto de Salud Pública de Navarra, IdiSNA, Navarre Institute for Health Research, REDISSEC, 31008, Pamplona, Spain.

Olle Melander (O)

Department of Clinical Sciences, Lund University, SE-221 00 Malmö, Sweden.

Sophia Harlid (S)

Department of Radiation Sciences, Oncology, Umea University, 901 87 Umea, Sweden.
ORCID: 0000-0001-8540-6891

Maria Nordendahl (M)

Department of Public Health and Clinical Medicine, Umea University, 901 87 Umea, Sweden.

Patrik Wennberg (P)

Department of Public Health and Clinical Medicine, Umea University, 901 87 Umea, Sweden.

Timothy J Key (TJ)

Nuffield Department of Population Health, University of Oxford, OX3 7LF Oxford, England.

Elio Riboli (E)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, SW7 2AZ London, UK.
ORCID: 0000-0001-6795-6080

Carmen Santiuste (C)

CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
Department of Epidemiology, Murcia Regional Health Authority, IMIB-Arrixaca, 30001 Murcia, Spain.

Rudolf Kaaks (R)

Division of Cancer Epidemiology, DKFZ, Foundation under Public Law, D-69120 Heidelberg, Germany.

Verena Katzke (V)

Division of Cancer Epidemiology, DKFZ, Foundation under Public Law, D-69120 Heidelberg, Germany.
ORCID: 0000-0002-6509-6555

Claudia Langenberg (C)

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, CB2 0SL Cambridge, UK.

Nicholas J Wareham (NJ)

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, CB2 0SL Cambridge, UK.

Heribert Schunkert (H)

Deutsches Herzzentrum München, Technische Universität München, 80636 Munich, Germany.
DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, 80636 Munich, Germany.
ORCID: 0000-0001-6428-3001

Jeanette Erdmann (J)

Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.

Christina Willenborg (C)

Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.

Christian Hengstenberg (C)

Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria.
ORCID: 0000-0002-8284-2994

Marcus E Kleber (ME)

Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0003-0663-7275

Graciela Delgado (G)

Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Winfried März (W)

Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Synlab Academy, Synlab Holding Deutschland GmbH, 68167 Mannheim, Germany.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.

Stavroula Kanoni (S)

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK.

George Dedoussis (G)

Department of Nutrition-Dietetics/Harokopio University, 17671 Athens, Greece.

Panos Deloukas (P)

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK.
Centre for Genomic Health, Queen Mary University of London, London E1 4NS, UK.
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
ORCID: 0000-0001-9251-070X

Majid Nikpay (M)

Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
ORCID: 0000-0003-0285-6454

Ruth McPherson (R)

Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
ORCID: 0000-0002-9087-6107

Markus Scholz (M)

Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.
LIFE Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.
ORCID: 0000-0002-4059-1779

Andrej Teren (A)

LIFE Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.
Heart Center Leipzig, 04289 Leipzig, Germany.

Adam S Butterworth (AS)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Yvonne T van der Schouw (YT)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA 3508 Utrecht, the Netherlands.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Genetically Determined Reproductive Aging and...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Genetically Determined Reproductive Aging and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genetically Determined Reproductive Aging and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetically Determined Reproductive Aging and...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Genetically Determined Reproductive Aging and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genetically Determined Reproductive Aging and...