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Genetic insights into biological mechanisms governing human ovarian ageing

Author

Listed:
  • Katherine S. Ruth

    (University of Exeter Medical School, University of Exeter)

  • Felix R. Day

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Jazib Hussain

    (University of Copenhagen)

  • Ana Martínez-Marchal

    (Universitat Autònoma de Barcelona
    Universitat Autònoma de Barcelona)

  • Catherine E. Aiken

    (University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome–MRC Institute of Metabolic Science, Addenbrooke’s Hospital
    University of Cambridge, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre)

  • Ajuna Azad

    (University of Copenhagen)

  • Deborah J. Thompson

    (University of Cambridge)

  • Lucie Knoblochova

    (Institute of Animal Physiology and Genetics of the Czech Academy of Sciences
    Charles University)

  • Hironori Abe

    (Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center)

  • Jane L. Tarry-Adkins

    (University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome–MRC Institute of Metabolic Science, Addenbrooke’s Hospital
    University of Cambridge, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre)

  • Javier Martin Gonzalez

    (University of Copenhagen)

  • Pierre Fontanillas

    (23andMe Inc.)

  • Annique Claringbould

    (Structural and Computational Biology Unit, EMBL)

  • Olivier B. Bakker

    (University of Groningen, University Medical Center Groningen, Department of Genetics)

  • Patrick Sulem

    (deCODE genetics/Amgen)

  • Robin G. Walters

    (University of Oxford
    University of Oxford)

  • Chikashi Terao

    (Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences
    Clinical Research Center, Shizuoka General Hospital
    University of Shizuoka)

  • Sandra Turon

    (Universitat Autònoma de Barcelona)

  • Momoko Horikoshi

    (Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences)

  • Kuang Lin

    (University of Oxford)

  • N. Charlotte Onland-Moret

    (University Medical Center Utrecht, Utrecht University)

  • Aditya Sankar

    (University of Copenhagen)

  • Emil Peter Thrane Hertz

    (University of Copenhagen
    The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Pascal N. Timshel

    (University of Copenhagen)

  • Vallari Shukla

    (University of Copenhagen)

  • Rehannah Borup

    (University of Copenhagen)

  • Kristina W. Olsen

    (University of Copenhagen
    Copenhagen University Hospital)

  • Paula Aguilera

    (University of Copenhagen
    Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Sevilla –Universidad Pablo de Olavide)

  • Mònica Ferrer-Roda

    (Universitat Autònoma de Barcelona
    Universitat Autònoma de Barcelona)

  • Yan Huang

    (Universitat Autònoma de Barcelona
    Universitat Autònoma de Barcelona)

  • Stasa Stankovic

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Paul R. H. J. Timmers

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Thomas U. Ahearn

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Behrooz Z. Alizadeh

    (University Medical Center Groningen, University of Groningen)

  • Elnaz Naderi

    (University Medical Center Groningen, University of Groningen)

  • Irene L. Andrulis

    (Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
    University of Toronto)

  • Alice M. Arnold

    (University of Washington)

  • Kristan J. Aronson

    (Queen’s University
    Cancer Research Institute, Queen’s University)

  • Annelie Augustinsson

    (Lund University)

  • Stefania Bandinelli

    (Geriatric Unit, Azienda Sanitaria Firenze (ASF))

  • Caterina M. Barbieri

    (Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute)

  • Robin N. Beaumont

    (University of Exeter Medical School, University of Exeter)

  • Heiko Becher

    (University Medical Center Hamburg-Eppendorf)

  • Matthias W. Beckmann

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg)

  • Stefania Benonisdottir

    (deCODE genetics/Amgen)

  • Sven Bergmann

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Murielle Bochud

    (University Center for Primary Care and Public Health, University of Lausanne)

  • Eric Boerwinkle

    (The University of Texas Health Science Center at Houston)

  • Stig E. Bojesen

    (Copenhagen University Hospital
    Copenhagen University Hospital
    University of Copenhagen)

  • Manjeet K. Bolla

    (University of Cambridge)

  • Dorret I. Boomsma

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health (APH) Research Institute
    Amsterdam Reproduction and Development (AR&D) Research Institute)

  • Nicholas Bowker

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Jennifer A. Brody

    (University of Washington)

  • Linda Broer

    (Erasmus MC)

  • Julie E. Buring

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Archie Campbell

    (University of Edinburgh)

  • Harry Campbell

    (University of Edinburgh)

  • Jose E. Castelao

    (Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS)

  • Eulalia Catamo

    (Institute for Maternal and Child Health – IRCCS ‘Burlo Garofolo’)

  • Stephen J. Chanock

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Georgia Chenevix-Trench

    (QIMR Berghofer Medical Research Institute)

  • Marina Ciullo

    (Institute of Genetics and Biophysics – CNR
    IRCCS Neuromed, Pozzilli)

  • Tanguy Corre

    (University of Lausanne
    Swiss Institute of Bioinformatics
    University Center for Primary Care and Public Health, University of Lausanne)

  • Fergus J. Couch

    (Mayo Clinic)

  • Angela Cox

    (University of Sheffield)

  • Laura Crisponi

    (Institute of Genetics and Biomedical Research, National Research Council)

  • Simon S. Cross

    (University of Sheffield)

  • Francesco Cucca

    (Institute of Genetics and Biomedical Research, National Research Council
    University of Sassari, Department of Biomedical Sciences)

  • Kamila Czene

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • George Davey Smith

    (University of Bristol
    University of Bristol)

  • Eco J. C. N. Geus

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health (APH) Research Institute
    Amsterdam Reproduction and Development (AR&D) Research Institute)

  • Renée Mutsert

    (Leiden University Medical Center)

  • Immaculata Vivo

    (Harvard T. H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Ellen W. Demerath

    (University of Minnesotta)

  • Joe Dennis

    (University of Cambridge)

  • Alison M. Dunning

    (University of Cambridge)

  • Miriam Dwek

    (University of Westminster)

  • Mikael Eriksson

    (Karolinska Institutet)

  • Tõnu Esko

    (Population and Medical Genetics, Broad Institute
    University of Tartu)

  • Peter A. Fasching

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg
    University of California at Los Angeles)

  • Jessica D. Faul

    (Survey Research Center, Institute for Social Research)

  • Luigi Ferrucci

    (Translational Gerontology Branch, National Institute on Aging)

  • Nora Franceschini

    (University of North Carolina)

  • Timothy M. Frayling

    (University of Exeter Medical School, University of Exeter)

  • Manuela Gago-Dominguez

    (Complejo Hospitalario Universitario de Santiago, SERGAS
    University of California San Diego)

  • Massimo Mezzavilla

    (University of Trieste)

  • Montserrat García-Closas

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Christian Gieger

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Graham G. Giles

    (Cancer Epidemiology Division, Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Harald Grallert

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Pascal Guénel

    (University Paris-Sud, University Paris-Saclay)

  • Christopher A. Haiman

    (University of Southern California)

  • Niclas Håkansson

    (Institute of Environmental Medicine, Karolinska Institutet)

  • Per Hall

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • Caroline Hayward

    (University of Edinburgh, Western General Hospital)

  • Chunyan He

    (University of Kentucky College of Medicine
    University of Kentucky Markey Cancer Center)

  • Wei He

    (Karolinska Institutet)

  • Gerardo Heiss

    (University of North Carolina)

  • Miya K. Høffding

    (University of Copenhagen)

  • John L. Hopper

    (The University of Melbourne)

  • Jouke J. Hottenga

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health (APH) Research Institute
    Amsterdam Reproduction and Development (AR&D) Research Institute)

  • Frank Hu

    (Harvard T. H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard T. H. Chan School of Public Health)

  • David Hunter

    (University of Oxford
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard T. H. Chan School of Public Health
    Harvard T. H. Chan School of Public Health)

  • Mohammad A. Ikram

    (Erasmus MC)

  • Rebecca D. Jackson

    (The Ohio State University)

  • Micaella D. R. Joaquim

    (University of Exeter Medical School, University of Exeter)

  • Esther M. John

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Peter K. Joshi

    (University of Edinburgh)

  • David Karasik

    (Harvard Medical School
    Hebrew SeniorLife Institute for Aging Research)

  • Sharon L. R. Kardia

    (University of Michigan)

  • Christiana Kartsonaki

    (University of Oxford
    University of Oxford)

  • Robert Karlsson

    (Karolinska Institutet)

  • Cari M. Kitahara

    (Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute)

  • Ivana Kolcic

    (University of Split)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Peter Kraft

    (Harvard T. H. Chan School of Public Health
    Harvard T. H. Chan School of Public Health)

  • Allison W. Kurian

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Zoltan Kutalik

    (Swiss Institute of Bioinformatics
    University Center for Primary Care and Public Health, University of Lausanne)

  • Martina Bianca

    (Institute for Maternal and Child Health – IRCCS ‘Burlo Garofolo’)

  • Genevieve LaChance

    (King’s College London)

  • Claudia Langenberg

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Lenore J. Launer

    (Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health)

  • Joop S. E. Laven

    (Erasmus University Medical Center)

  • Deborah A. Lawlor

    (University of Bristol
    University of Bristol)

  • Loic Marchand

    (University of Hawaii Cancer Center)

  • Jingmei Li

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • Annika Lindblom

    (Karolinska Institutet
    Karolinska University Hospital)

  • Sara Lindstrom

    (University of Washington)

  • Tricia Lindstrom

    (Mayo Clinic)

  • Martha Linet

    (Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute)

  • YongMei Liu

    (Wake Forest School of Medicine)

  • Simin Liu

    (Brown University
    Brown University)

  • Jian’an Luan

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Reedik Mägi

    (University of Tartu)

  • Patrik K. E. Magnusson

    (Karolinska Institutet)

  • Massimo Mangino

    (King’s College London
    NIHR Biomedical Research Centre at Guy’s and St. Thomas’ Foundation Trust)

  • Arto Mannermaa

    (University of Eastern Finland
    University of Eastern Finland
    Kuopio University Hospital)

  • Brumat Marco

    (University of Trieste)

  • Jonathan Marten

    (University of Edinburgh, Western General Hospital)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Insititute)

  • Hamdi Mbarek

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health (APH) Research Institute
    Amsterdam Reproduction and Development (AR&D) Research Institute)

  • Barbara McKnight

    (University of Washington)

  • Sarah E. Medland

    (QIMR Berghofer Medical Research Insititute)

  • Christa Meisinger

    (Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health
    Central Hospital of Augsburg, MONICA/KORA Myocardial Infarction Registry)

  • Thomas Meitinger

    (German Research Center for Environmental Health)

  • Cristina Menni

    (King’s College London)

  • Andres Metspalu

    (University of Tartu)

  • Lili Milani

    (University of Tartu)

  • Roger L. Milne

    (Cancer Epidemiology Division, Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Grant W. Montgomery

    (The University of Queensland)

  • Dennis O. Mook-Kanamori

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Antonella Mulas

    (Institute of Genetics and Biomedical Research, National Research Council)

  • Anna M. Mulligan

    (University of Toronto
    University Health Network)

  • Alison Murray

    (University of Aberdeen)

  • Mike A. Nalls

    (National Institutes of Health)

  • Anne Newman

    (University of Pittsburgh
    University of Pittsburgh)

  • Raymond Noordam

    (Leiden University Medical Center)

  • Teresa Nutile

    (Institute of Genetics and Biophysics – CNR)

  • Dale R. Nyholt

    (Queensland University of Technology)

  • Andrew F. Olshan

    (University of North Carolina at Chapel Hill)

  • Håkan Olsson

    (Lund University)

  • Jodie N. Painter

    (QIMR Berghofer Medical Research Insititute)

  • Alpa V. Patel

    (American Cancer Society)

  • Nancy L. Pedersen

    (Karolinska Institutet)

  • Natalia Perjakova

    (University of Tartu)

  • Annette Peters

    (Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Ulrike Peters

    (Fred Hutchinson Cancer Research Center)

  • Paul D. P. Pharoah

    (University of Cambridge
    University of Cambridge)

  • Ozren Polasek

    (University of Split
    Gen-Info Ltd)

  • Eleonora Porcu

    (Institute of Genetics and Biomedical Research, National Research Council)

  • Bruce M. Psaty

    (University of Washington)

  • Iffat Rahman

    (Quantify Research)

  • Gad Rennert

    (Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine)

  • Hedy S. Rennert

    (Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine)

  • Paul M. Ridker

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Susan M. Ring

    (University of Bristol
    University of Bristol)

  • Antonietta Robino

    (Institute for Maternal and Child Health – IRCCS ‘Burlo Garofolo’)

  • Lynda M. Rose

    (Brigham and Women’s Hospital)

  • Frits R. Rosendaal

    (Leiden University Medical Center)

  • Jacques Rossouw

    (Women’s Health Initiative Branch, National Heart, Lung, and Blood Institute)

  • Igor Rudan

    (University of Edinburgh)

  • Rico Rueedi

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Daniela Ruggiero

    (Institute of Genetics and Biophysics – CNR
    IRCCS Neuromed, Pozzilli)

  • Cinzia F. Sala

    (Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute)

  • Emmanouil Saloustros

    (University Hospital of Larissa)

  • Dale P. Sandler

    (Epidemiology Branch, National Institute of Environmental Health Sciences, NIH)

  • Serena Sanna

    (Institute of Genetics and Biomedical Research, National Research Council)

  • Elinor J. Sawyer

    (Guy’s Campus, King’s College London)

  • Chloé Sarnowski

    (Boston University School of Public Health)

  • David Schlessinger

    (Intramural Research Program)

  • Marjanka K. Schmidt

    (The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital
    The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital)

  • Minouk J. Schoemaker

    (The Institute of Cancer Research)

  • Katharina E. Schraut

    (University of Edinburgh
    University of Edinburgh, Royal Infirmary of Edinburgh)

  • Christopher Scott

    (Mayo Clinic)

  • Saleh Shekari

    (University of Exeter Medical School, University of Exeter)

  • Amruta Shrikhande

    (University of Copenhagen)

  • Albert V. Smith

    (Icelandic Heart Association
    University of Iceland)

  • Blair H. Smith

    (University of Dundee)

  • Jennifer A. Smith

    (University of Michigan)

  • Rossella Sorice

    (Institute of Genetics and Biophysics – CNR)

  • Melissa C. Southey

    (Cancer Epidemiology Division, Cancer Council Victoria
    Monash University
    The University of Melbourne)

  • Tim D. Spector

    (King’s College London)

  • John J. Spinelli

    (Population Oncology, BC Cancer
    University of British Columbia)

  • Meir Stampfer

    (Harvard T. H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard T. H. Chan School of Public Health)

  • Doris Stöckl

    (Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health
    Ludwig-Maximilians-Universität)

  • Joyce B. J. Meurs

    (Erasmus MC)

  • Konstantin Strauch

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health
    Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich
    University Medical Center, Johannes Gutenberg University)

  • Unnur Styrkarsdottir

    (deCODE genetics/Amgen)

  • Anthony J. Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Toshiko Tanaka

    (Translational Gerontology Branch, National Institute on Aging)

  • Lauren R. Teras

    (American Cancer Society)

  • Alexander Teumer

    (University Medicine Greifswald)

  • Unnur Þorsteinsdottir

    (deCODE genetics/Amgen
    University of Iceland)

  • Nicholas J. Timpson

    (University of Bristol
    University of Bristol)

  • Daniela Toniolo

    (Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute)

  • Michela Traglia

    (Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute)

  • Melissa A. Troester

    (University of North Carolina at Chapel Hill)

  • Thérèse Truong

    (University Paris-Sud, University Paris-Saclay)

  • Jessica Tyrrell

    (University of Exeter Medical School, University of Exeter)

  • André G. Uitterlinden

    (Erasmus MC
    Erasmus MC)

  • Sheila Ulivi

    (Institute for Maternal and Child Health – IRCCS ‘Burlo Garofolo’)

  • Celine M. Vachon

    (Mayo Clinic)

  • Veronique Vitart

    (University of Edinburgh, Western General Hospital)

  • Uwe Völker

    (University Medicine Greifswald)

  • Peter Vollenweider

    (Lausanne University Hospital and University of Lausanne)

  • Henry Völzke

    (University Medicine Greifswald)

  • Qin Wang

    (University of Cambridge)

  • Nicholas J. Wareham

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Clarice R. Weinberg

    (Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH)

  • David R. Weir

    (Survey Research Center, Institute for Social Research)

  • Amber N. Wilcox

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Ko Willems Dijk

    (Leiden University Medical Center
    Leiden University Medical Center
    Leiden University Medical Center)

  • Gonneke Willemsen

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health (APH) Research Institute
    Amsterdam Reproduction and Development (AR&D) Research Institute)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Bruce H. R. Wolffenbuttel

    (University Medical Center Groningen, University of Groningen)

  • Alicja Wolk

    (Institute of Environmental Medicine, Karolinska Institutet
    Uppsala University)

  • Andrew R. Wood

    (University of Exeter Medical School, University of Exeter)

  • Wei Zhao

    (University of Michigan)

  • Marek Zygmunt

    (University Medicine Greifswald)

  • Zhengming Chen

    (University of Oxford
    University of Oxford)

  • Liming Li

    (Peking University Health Science Center
    Peking University Center for Public Health and Epidemic Preparedness & Response)

  • Lude Franke

    (University of Groningen, University Medical Center Groningen, Department of Genetics
    Oncode Institute)

  • Stephen Burgess

    (University of Cambridge
    University of Cambridge)

  • Patrick Deelen

    (University of Groningen, University Medical Center Groningen, Department of Genetics
    University Medical Centre Utrecht)

  • Tune H. Pers

    (University of Copenhagen)

  • Marie Louise Grøndahl

    (Copenhagen University Hospital)

  • Claus Yding Andersen

    (Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen)

  • Anna Pujol

    (Universitat Autònoma de Barcelona)

  • Andres J. Lopez-Contreras

    (University of Copenhagen
    Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC) – Universidad de Sevilla –Universidad Pablo de Olavide)

  • Jeremy A. Daniel

    (The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Kari Stefansson

    (deCODE genetics/Amgen
    University of Iceland)

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf)

  • Yvonne T. van der Schouw

    (University Medical Center Utrecht, Utrecht University)

  • Kathryn L. Lunetta

    (Boston University School of Public Health
    NHLBI’s and Boston University’s Framingham Heart Study)

  • Daniel I. Chasman

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Douglas F. Easton

    (University of Cambridge
    University of Cambridge)

  • Jenny A. Visser

    (Erasmus MC)

  • Susan E. Ozanne

    (University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome–MRC Institute of Metabolic Science, Addenbrooke’s Hospital)

  • Satoshi H. Namekawa

    (Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center)

  • Petr Solc

    (Institute of Animal Physiology and Genetics of the Czech Academy of Sciences)

  • Joanne M. Murabito

    (NHLBI’s and Boston University’s Framingham Heart Study
    Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine)

  • Ken K. Ong

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
    University of Cambridge)

  • Eva R. Hoffmann

    (University of Copenhagen)

  • Anna Murray

    (University of Exeter Medical School, University of Exeter)

  • Ignasi Roig

    (Universitat Autònoma de Barcelona
    Universitat Autònoma de Barcelona)

  • John R. B. Perry

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
    Erasmus MC)

Abstract

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

Suggested Citation

  • Katherine S. Ruth & Felix R. Day & Jazib Hussain & Ana Martínez-Marchal & Catherine E. Aiken & Ajuna Azad & Deborah J. Thompson & Lucie Knoblochova & Hironori Abe & Jane L. Tarry-Adkins & Javier Marti, 2021. "Genetic insights into biological mechanisms governing human ovarian ageing," Nature, Nature, vol. 596(7872), pages 393-397, August.
    • Handle: RePEc:nat:nature:v:596:y:2021:i:7872:d:10.1038_s41586-021-03779-7
    DOI: 10.1038/s41586-021-03779-7
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    1. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis," IJERPH, MDPI, vol. 19(24), pages 1-57, December.
    2. Gemma L. Clayton & Maria Carolina Borges & Deborah A. Lawlor, 2024. "The impact of reproductive factors on the metabolic profile of females from menarche to menopause," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Xiao-Yu He & Bang-Sheng Wu & Liu Yang & Yu Guo & Yue-Ting Deng & Ze-Yu Li & Chen-Jie Fei & Wei-Shi Liu & Yi-Jun Ge & Jujiao Kang & Jianfeng Feng & Wei Cheng & Qiang Dong & Jin-Tai Yu, 2024. "Genetic associations of protein-coding variants in venous thromboembolism," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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