Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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34349265
TITLE
Genetic insights into biological mechanisms governing human ovarian ageing.
ABSTRACT
Reproductive longevity is essential for fertility and influences healthy ageing in women , 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 premutations . 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.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
DATE PUBLISHED
2021 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/08/24
accepted 2021/06/29
pubmed 2021/08/06 06:00
medline 2021/08/06 06:00
entrez 2021/08/05 06:19
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ruth KS Ruth Katherine S KS Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Day FR Day Felix R FR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Hussain J Hussain Jazib J DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Martínez-Marchal A Martínez-Marchal Ana A Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Aiken CE Aiken Catherine E CE Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Azad A Azad Ajuna A DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Thompson DJ Thompson Deborah J DJ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Knoblochova L Knoblochova Lucie L Faculty of Science, Charles University, Prague, Czech Republic.
Abe H Abe Hironori H Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Tarry-Adkins JL Tarry-Adkins Jane L JL Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Gonzalez JM Gonzalez Javier Martin JM Transgenic Core Facility, Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Fontanillas P Fontanillas Pierre P 23andMe Inc., Sunnyvale, CA, USA.
Claringbould A Claringbould Annique A Structural and Computational Biology Unit, EMBL, Heidelberg, Germany.
Bakker OB Bakker Olivier B OB University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
Sulem P Sulem Patrick P deCODE genetics/Amgen, Reykjavik, Iceland.
Walters RG Walters Robin G RG MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Terao C Terao Chikashi C Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Turon S Turon Sandra S Transgenic Animal Unit, Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Horikoshi M Horikoshi Momoko M Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Lin K Lin Kuang K Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Onland-Moret NC Onland-Moret N Charlotte NC Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Sankar A Sankar Aditya A DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Hertz EPT Hertz Emil Peter Thrane EPT The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Timshel PN Timshel Pascal N PN The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Shukla V Shukla Vallari V DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Borup R Borup Rehannah R DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Olsen KW Olsen Kristina W KW Reproductive Medicine, Department of Obstetrics and Gynaecology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Aguilera P Aguilera Paula P Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de Sevilla -Universidad Pablo de Olavide, Seville, Spain.
Ferrer-Roda M Ferrer-Roda Mònica M Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Huang Y Huang Yan Y Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Stankovic S Stankovic Stasa S MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Timmers PRHJ Timmers Paul R H J PRHJ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Ahearn TU Ahearn Thomas U TU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Alizadeh BZ Alizadeh Behrooz Z BZ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Naderi E Naderi Elnaz E Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Andrulis IL Andrulis Irene L IL Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Arnold AM Arnold Alice M AM Department of Biostatistics, University of Washington, Seattle, WA, USA.
Aronson KJ Aronson Kristan J KJ Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Augustinsson A Augustinsson Annelie A Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
Bandinelli S Bandinelli Stefania S Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
Barbieri CM Barbieri Caterina M CM Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Beaumont RN Beaumont Robin N RN Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Becher H Becher Heiko H Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Beckmann MW Beckmann Matthias W MW Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Benonisdottir S Benonisdottir Stefania S deCODE genetics/Amgen, Reykjavik, Iceland.
Bergmann S Bergmann Sven S Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Bochud M Bochud Murielle M University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Boerwinkle E Boerwinkle Eric E Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Bojesen SE Bojesen Stig E SE Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bolla MK Bolla Manjeet K MK Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Boomsma DI Boomsma Dorret I DI Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, The Netherlands.
Bowker N Bowker Nicholas N MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Brody JA Brody Jennifer A JA Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
Broer L Broer Linda L Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Buring JE Buring Julie E JE Harvard Medical School, Boston, MA, USA.
Campbell A Campbell Archie A Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Campbell H Campbell Harry H Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Castelao JE Castelao Jose E JE Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
Catamo E Catamo Eulalia E Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Chanock SJ Chanock Stephen J SJ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Chenevix-Trench G Chenevix-Trench Georgia G Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ciullo M Ciullo Marina M IRCCS Neuromed, Pozzilli, Isernia, Italy.
Corre T Corre Tanguy T University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Couch FJ Couch Fergus J FJ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Cox A Cox Angela A Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Crisponi L Crisponi Laura L Institute of Genetics and Biomedical Research, National Research Council, Cagliari, Italy.
Cross SS Cross Simon S SS Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Cucca F Cucca Francesco F University of Sassari, Department of Biomedical Sciences, Sassari, Italy.
Czene K Czene Kamila K Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
Smith GD Smith George Davey GD Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
de Geus EJCN de Geus Eco J C N EJCN Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, The Netherlands.
de Mutsert R de Mutsert Renée R Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
De Vivo I De Vivo Immaculata I Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Demerath EW Demerath Ellen W EW Division of Epidemiology & Community Health, University of Minnesotta, Minneapolis, MN, USA.
Dennis J Dennis Joe J Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Dunning AM Dunning Alison M AM Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Dwek M Dwek Miriam M School of Life Sciences, University of Westminster, London, UK.
Eriksson M Eriksson Mikael M Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Esko T Esko Tõnu T Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Fasching PA Fasching Peter A PA David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA.
Faul JD Faul Jessica D JD Survey Research Center, Institute for Social Research, Ann Arbor, MI, USA.
Ferrucci L Ferrucci Luigi L Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Franceschini N Franceschini Nora N Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Frayling TM Frayling Timothy M TM Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Gago-Dominguez M Gago-Dominguez Manuela M Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Mezzavilla M Mezzavilla Massimo M Department of Medical Sciences, University of Trieste, Trieste, Italy.
García-Closas M García-Closas Montserrat M Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Gieger C Gieger Christian C German Center for Diabetes Research (DZD), Neuherberg, Germany.
Giles GG Giles Graham G GG Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Grallert H Grallert Harald H German Center for Diabetes Research (DZD), Neuherberg, Germany.
Gudbjartsson DF Gudbjartsson Daniel F DF deCODE genetics/Amgen, Reykjavik, Iceland.
Gudnason V Gudnason Vilmundur V Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Guénel P Guénel Pascal P Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
Haiman CA Haiman Christopher A CA Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Håkansson N Håkansson Niclas N Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Hall P Hall Per P Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
Hayward C Hayward Caroline C MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
He C He Chunyan C The Cancer Prevention and Control Research Program, University of Kentucky Markey Cancer Center, Lexington, KY, USA.
He W He Wei W Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Heiss G Heiss Gerardo G Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Høffding MK Høffding Miya K MK DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Hopper JL Hopper John L JL Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Hottenga JJ Hottenga Jouke J JJ Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, The Netherlands.
Hu F Hu Frank F Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Hunter D Hunter David D Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ikram MA Ikram Mohammad A MA Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Jackson RD Jackson Rebecca D RD Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Joaquim MDR Joaquim Micaella D R MDR Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
John EM John Esther M EM Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Joshi PK Joshi Peter K PK Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Karasik D Karasik David D Hebrew SeniorLife Institute for Aging Research, Boston, MA, USA.
Kardia SLR Kardia Sharon L R SLR Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Kartsonaki C Kartsonaki Christiana C MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Karlsson R Karlsson Robert R Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kitahara CM Kitahara Cari M CM Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Kolcic I Kolcic Ivana I Faculty of Medicine, University of Split, Split, Croatia.
Kooperberg C Kooperberg Charles C Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kraft P Kraft Peter P Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Kurian AW Kurian Allison W AW Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Kutalik Z Kutalik Zoltan Z University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
La Bianca M La Bianca Martina M Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
LaChance G LaChance Genevieve G Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Langenberg C Langenberg Claudia C MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Launer LJ Launer Lenore J LJ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
Laven JSE Laven Joop S E JSE Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Lawlor DA Lawlor Deborah A DA Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
Le Marchand L Le Marchand Loic L Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Li J Li Jingmei J Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
Lindblom A Lindblom Annika A Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Lindstrom S Lindstrom Sara S Department of Epidemiology, University of Washington, Seattle, WA, USA.
Lindstrom T Lindstrom Tricia T Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Linet M Linet Martha M Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Liu Y Liu YongMei Y Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Wake Forest, NC, USA.
Liu S Liu Simin S Department of Medicine, Brown University, Providence, RI, USA.
Luan J Luan Jian'an J MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Mägi R Mägi Reedik R Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Magnusson PKE Magnusson Patrik K E PKE Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mangino M Mangino Massimo M NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, UK.
Mannermaa A Mannermaa Arto A Biobank of Eastern Finland, Kuopio University Hospital, Kuopio, Finland.
Marco B Marco Brumat B Department of Medical Sciences, University of Trieste, Trieste, Italy.
Marten J Marten Jonathan J MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Insititute, Brisbane, Queensland, Australia.
Mbarek H Mbarek Hamdi H Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, The Netherlands.
McKnight B McKnight Barbara B Department of Biostatistics, University of Washington, Seattle, WA, USA.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Insititute, Brisbane, Queensland, Australia.
Meisinger C Meisinger Christa C Central Hospital of Augsburg, MONICA/KORA Myocardial Infarction Registry, Augsburg, Germany.
Meitinger T Meitinger Thomas T Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Menni C Menni Cristina C Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Metspalu A Metspalu Andres A Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Milani L Milani Lili L Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Milne RL Milne Roger L RL Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Mook-Kanamori DO Mook-Kanamori Dennis O DO Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
Mulas A Mulas Antonella A Institute of Genetics and Biomedical Research, National Research Council, Cagliari, Italy.
Mulligan AM Mulligan Anna M AM Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
Murray A Murray Alison A The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK.
Nalls MA Nalls Mike A MA Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Newman A Newman Anne A Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Noordam R Noordam Raymond R Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Nutile T Nutile Teresa T Institute of Genetics and Biophysics - CNR, Naples, Italy.
Nyholt DR Nyholt Dale R DR Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
Olshan AF Olshan Andrew F AF Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Olsson H Olsson Håkan H Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
Painter JN Painter Jodie N JN QIMR Berghofer Medical Research Insititute, Brisbane, Queensland, Australia.
Patel AV Patel Alpa V AV Department of Population Science, American Cancer Society, Atlanta, GA, USA.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Perjakova N Perjakova Natalia N Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Peters A Peters Annette A German Center for Diabetes Research (DZD), Neuherberg, Germany.
Peters U Peters Ulrike U Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Pharoah PDP Pharoah Paul D P PDP Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Polasek O Polasek Ozren O Gen-Info Ltd, Zagreb, Croatia.
Porcu E Porcu Eleonora E Institute of Genetics and Biomedical Research, National Research Council, Cagliari, Italy.
Psaty BM Psaty Bruce M BM Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
Rahman I Rahman Iffat I Quantify Research, Stockholm, Sweden.
Rennert G Rennert Gad G Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
Rennert HS Rennert Hedy S HS Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
Ridker PM Ridker Paul M PM Harvard Medical School, Boston, MA, USA.
Ring SM Ring Susan M SM Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
Robino A Robino Antonietta A Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Rose LM Rose Lynda M LM Brigham and Women's Hospital, Boston, MA, USA.
Rosendaal FR Rosendaal Frits R FR Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Rossouw J Rossouw Jacques J Women's Health Initiative Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
Rudan I Rudan Igor I Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Rueedi R Rueedi Rico R Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Ruggiero D Ruggiero Daniela D IRCCS Neuromed, Pozzilli, Isernia, Italy.
Sala CF Sala Cinzia F CF Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Saloustros E Saloustros Emmanouil E Department of Oncology, University Hospital of Larissa, Larissa, Greece.
Sandler DP Sandler Dale P DP Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Sanna S Sanna Serena S Institute of Genetics and Biomedical Research, National Research Council, Cagliari, Italy.
Sawyer EJ Sawyer Elinor J EJ School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, UK.
Sarnowski C Sarnowski Chloé C Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Schlessinger D Schlessinger David D National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Schmidt MK Schmidt Marjanka K MK Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Schoemaker MJ Schoemaker Minouk J MJ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Schraut KE Schraut Katharina E KE Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.
Scott C Scott Christopher C Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Shekari S Shekari Saleh S Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Shrikhande A Shrikhande Amruta A DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Smith AV Smith Albert V AV Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Smith BH Smith Blair H BH Division of Population and Health Genomics, University of Dundee, Dundee, UK.
Smith JA Smith Jennifer A JA Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Sorice R Sorice Rossella R Institute of Genetics and Biophysics - CNR, Naples, Italy.
Southey MC Southey Melissa C MC Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Spinelli JJ Spinelli John J JJ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
Stampfer M Stampfer Meir M Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Stöckl D Stöckl Doris D Department of Obstetrics and Gynaecology, Campus Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
van Meurs JBJ van Meurs Joyce B J JBJ Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Strauch K Strauch Konstantin K Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Styrkarsdottir U Styrkarsdottir Unnur U deCODE genetics/Amgen, Reykjavik, Iceland.
Swerdlow AJ Swerdlow Anthony J AJ Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Tanaka T Tanaka Toshiko T Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Teras LR Teras Lauren R LR Department of Population Science, American Cancer Society, Atlanta, GA, USA.
Teumer A Teumer Alexander A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Þorsteinsdottir U Þorsteinsdottir Unnur U Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Timpson NJ Timpson Nicholas J NJ Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
Toniolo D Toniolo Daniela D Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Traglia M Traglia Michela M Genetics of Common Disorders Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Troester MA Troester Melissa A MA Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Truong T Truong Thérèse T Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
Tyrrell J Tyrrell Jessica J Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Uitterlinden AG Uitterlinden André G AG Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Ulivi S Ulivi Sheila S Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Vachon CM Vachon Celine M CM Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Vitart V Vitart Veronique V MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Völker U Völker Uwe U Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Vollenweider P Vollenweider Peter P Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Völzke H Völzke Henry H Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Wang Q Wang Qin Q Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Wareham NJ Wareham Nicholas J NJ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Weinberg CR Weinberg Clarice R CR Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Weir DR Weir David R DR Survey Research Center, Institute for Social Research, Ann Arbor, MI, USA.
Wilcox AN Wilcox Amber N AN Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
van Dijk KW van Dijk Ko Willems KW Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Willemsen G Willemsen Gonneke G Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, The Netherlands.
Wilson JF Wilson James F JF MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Wolffenbuttel BHR Wolffenbuttel Bruce H R BHR Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Wolk A Wolk Alicja A Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Wood AR Wood Andrew R AR Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Zhao W Zhao Wei W Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Zygmunt M Zygmunt Marek M Department of Obstetrics and Gynecology, University Medicine Greifswald, Greifswald, Germany.
Biobank-based Integrative Omics Study (BIOS) Consortium
eQTLGen Consortium
Biobank Japan Project
China Kadoorie Biobank Collaborative Group
kConFab Investigators
LifeLines Cohort Study
InterAct consortium
23andMe Research Team
Chen Z Chen Zhengming Z MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Li L Li Liming L Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, P.R. China.
Franke L Franke Lude L Oncode Institute, Utrecht, The Netherlands.
Burgess S Burgess Stephen S MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Deelen P Deelen Patrick P Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
Pers TH Pers Tune H TH The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Grøndahl ML Grøndahl Marie Louise ML Reproductive Medicine, Department of Obstetrics and Gynaecology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Andersen CY Andersen Claus Yding CY Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Pujol A Pujol Anna A Transgenic Animal Unit, Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Lopez-Contreras AJ Lopez-Contreras Andres J AJ Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC) - Universidad de Sevilla -Universidad Pablo de Olavide, Seville, Spain.
Daniel JA Daniel Jeremy A JA The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Stefansson K Stefansson Kari K Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Chang-Claude J Chang-Claude Jenny J Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
van der Schouw YT van der Schouw Yvonne T YT Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Lunetta KL Lunetta Kathryn L KL NHLBI's and Boston University's Framingham Heart Study, Framingham, MA, USA.
Chasman DI Chasman Daniel I DI Harvard Medical School, Boston, MA, USA.
Easton DF Easton Douglas F DF Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Visser JA Visser Jenny A JA Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Ozanne SE Ozanne Susan E SE University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Namekawa SH Namekawa Satoshi H SH Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Solc P Solc Petr P Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Libechov, Czech Republic.
Murabito JM Murabito Joanne M JM Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, MA, USA.
Ong KK Ong Ken K KK Department of Paediatrics, University of Cambridge, Cambridge, UK.
Hoffmann ER Hoffmann Eva R ER DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. eva@sund.ku.dk.
Murray A Murray Anna A Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK. a.murray@exeter.ac.uk.
Roig I Roig Ignasi I Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. ignasi.roig@uab.cat.
Perry JRB Perry John R B JRB Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. john.perry@mrc-epid.cam.ac.uk.
INVESTIGATORS
JOURNAL
VOLUME: 596
ISSUE: 7872
TITLE: Nature
ISOABBREVIATION: Nature
YEAR: 2021
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-4687
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nature
COUNTRY: England
ISSNLINKING: 0028-0836
NLMUNIQUEID: 0410462
PUBLICATION TYPE
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Journal Article
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R01 HL105756 NHLBI NIH HHS United States
U01 HL130114 NHLBI NIH HHS United States
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