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dc.contributor.authorDam, Veerle
dc.contributor.authorOnland-Moret, N Charlotte
dc.contributor.authorBurgess, Stephen
dc.contributor.authorChirlaque, Maria-Dolores
dc.contributor.authorPeters, Sanne AE
dc.contributor.authorSchuit, Ewoud
dc.contributor.authorTikk, Kaja
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorOliver-Williams, Clare
dc.contributor.authorWood, Angela
dc.contributor.authorTjønneland, Anne
dc.contributor.authorDahm, Christina C
dc.contributor.authorOvervad, Kim
dc.contributor.authorBoutron-Ruault, Marie-Christine
dc.contributor.authorSchulze, Matthias B
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorFerrari, Pietro
dc.contributor.authorMasala, Giovanna
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorTumino, Rosario
dc.contributor.authorMatullo, Giuseppe
dc.contributor.authorPanico, Salvatore
dc.contributor.authorBoer, Jolanda MA
dc.contributor.authorVerschuren, WM Monique
dc.contributor.authorWaaseth, Marit
dc.contributor.authorSánchez Pérez, Maria José
dc.contributor.authorAmiano, Pilar
dc.contributor.authorImaz, Liher
dc.contributor.authorMoreno-Iribas, Conchi
dc.contributor.authorMelander, Olle
dc.contributor.authorHarlid, Sophia
dc.contributor.authorNordendahl, Maria
dc.contributor.authorWennberg, Patrik
dc.contributor.authorKey, Timothy J
dc.contributor.authorRiboli, Elio
dc.contributor.authorSantiuste, Carmen
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKatzke, Verena
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorWareham, Nicholas
dc.contributor.authorSchunkert, Heribert
dc.contributor.authorErdmann, Jeanette
dc.contributor.authorWillenborg, Christina
dc.contributor.authorHengstenberg, Christian
dc.contributor.authorKleber, Marcus E
dc.contributor.authorDelgado, Graciela
dc.contributor.authorMärz, Winfried
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorDedoussis, George
dc.contributor.authorDeloukas, Panos
dc.contributor.authorNikpay, Majid
dc.contributor.authorMcPherson, Ruth
dc.contributor.authorScholz, Markus
dc.contributor.authorTeren, Andrej
dc.contributor.authorButterworth, Adam S
dc.contributor.authorvan der Schouw, Yvonne T
dc.date.accessioned2022-05-09T23:30:14Z
dc.date.available2022-05-09T23:30:14Z
dc.date.issued2022-03-20
dc.identifier.issn0021-972X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336942
dc.description.abstractBACKGROUND: 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 four 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 GWAS 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 Estimate (RRE)IVW=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.
dc.format.mediumPrint-Electronic
dc.publisherThe Endocrine Society
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectMendelian Randomization
dc.subjectReproductive aging
dc.subjectcoronary heart disease
dc.subjectrisk factors
dc.titleGenetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization.
dc.typeArticle
dc.publisher.departmentMrc Biostatistics Unit
dc.publisher.departmentDepartment of Public Health And Primary Care, Cardiovascular Epidemiology Unit
dc.publisher.departmentMrc Epidemiology Unit
dc.publisher.departmentoffice of The School of Clinical Medicine
dc.date.updated2022-05-03T11:54:17Z
prism.publicationDate2022
prism.publicationNameJ Clin Endocrinol Metab
dc.identifier.doi10.17863/CAM.84365
dcterms.dateAccepted2022-03-16
rioxxterms.versionofrecord10.1210/clinem/dgac171
rioxxterms.versionAM
dc.contributor.orcidDam, Veerle [0000-0002-5982-232X]
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.contributor.orcidChirlaque, Maria-Dolores [0000-0001-9242-3040]
dc.contributor.orcidSchuit, Ewoud [0000-0002-9548-3214]
dc.contributor.orcidWeiderpass, Elisabete [0000-0003-2237-0128]
dc.contributor.orcidWood, Angela [0000-0002-7937-304X]
dc.contributor.orcidOvervad, Kim [0000-0001-6429-7921]
dc.contributor.orcidBoutron-Ruault, Marie-Christine [0000-0002-5956-5693]
dc.contributor.orcidTrichopoulou, Antonia [0000-0002-7204-6396]
dc.contributor.orcidFerrari, Pietro [0000-0001-9358-7338]
dc.contributor.orcidMasala, Giovanna [0000-0002-5758-9069]
dc.contributor.orcidKrogh, Vittorio [0000-0003-0122-8624]
dc.contributor.orcidPanico, Salvatore [0000-0002-5498-8312]
dc.contributor.orcidHarlid, Sophia [0000-0001-8540-6891]
dc.contributor.orcidRiboli, Elio [0000-0001-6795-6080]
dc.contributor.orcidKatzke, Verena [0000-0002-6509-6555]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidSchunkert, Heribert [0000-0001-6428-3001]
dc.contributor.orcidHengstenberg, Christian [0000-0002-8284-2994]
dc.contributor.orcidKleber, Marcus E [0000-0003-0663-7275]
dc.contributor.orcidDeloukas, Panos [0000-0001-9251-070X]
dc.contributor.orcidNikpay, Majid [0000-0003-0285-6454]
dc.contributor.orcidMcPherson, Ruth [0000-0002-9087-6107]
dc.contributor.orcidScholz, Markus [0000-0002-4059-1779]
dc.identifier.eissn1945-7197
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (MC_UU_00006/1)
pubs.funder-project-idMedical Research Council (G0800270)
pubs.funder-project-idEuropean Research Council (268834)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MC_UU_12015/5)
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
cam.issuedOnline2022-03-20
cam.orpheus.success2022-05-09 - Embargo set during processing via Fast-track
cam.depositDate2022-05-03
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2023-03-20


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