Evidence map›Paper›PMID 26414677›Full record

ArticleNature genetics2015

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Felix R Day, Katherine S Ruth, Deborah J Thompson, Kathryn L Lunetta, Natalia Pervjakova, Daniel I Chasman, Lisette Stolk, Hilary K Finucane, Patrick Sulem, Brendan Bulik-Sullivan and 237 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
248citing papers in PubMed, 11 pooled it
16.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

248 citing papers in PubMed, 11 syntheses or guidelines pooled it, 442 citations in OpenAlex.

  1. Pooled it
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  9. Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Pooled it
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  15. Polymorphism of theLife (Basel, Switzerland) · 2026
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188 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

247 authors at 20 institutions in 21 countries.

Felix R Day *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Katherine S Ruth *Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Deborah J Thompson *Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Kathryn L LunettaBoston University School of Public Health, Department of Biostatistics. Boston, Massachusetts 02118, USA.
Natalia PervjakovaEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Lisette StolkDepartment of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
Hilary K FinucaneDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Patrick SulemdeCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
Brendan Bulik-SullivanStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Andrew D JohnsonNHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
Cathy E ElksMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Nora FranceschiniDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Chunyan HeDepartment of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN 46202, USA.
Elisabeth AltmaierResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle Washington 98101 USA.
Lude L FrankeDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Jennifer E HuffmanNHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
Margaux F KellerMerck Pharmaceuticals, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
Patrick F McArdleProgram in Personalized Medicine, Division of Endocrinology, Diabetes and Nutrition - University of Maryland School of Medicine, USA. Baltimore, MD 21201.
Teresa NutileInstitute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
Eleonora PorcuInstitute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
Antonietta RobinoInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Lynda M RoseDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Ursula M SchickFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
Michela TragliaDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
Dragana VuckovicInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Jie YaoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Eva AlbrechtInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Najaf AminGenetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
Tanguy CorreDepartment of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.
Jouke-Jan HottengaDepartment of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Massimo ManginoDepartment of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
Albert V SmithIcelandic Heart Association, Kopavogur, Iceland.
Toshiko TanakaLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21224, United States of America.
Goncalo AbecasisCenter for Statistical Genetics, Ann Arbor, University of Michigan, Michigan 48109-2029, USA.
Irene L AndrulisLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Hoda Anton-CulverDepartment of Epidemiology, University of California Irvine, Irvine, California, USA.
Antonis C AntoniouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Volker ArndtDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Alice M ArnoldDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Caterina BarbieriInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Matthias W BeckmannDepartment of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Alicia Beeghly-FadielDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Javier BenitezHuman Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Leslie BernsteinBeckman Research Institute of City of Hope, Duarte, CA, USA.
Suzette J BielinskiDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Carl BlomqvistDepartment of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Eric BoerwinkleHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Natalia V BogdanovaDepartment of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Stig E BojesenFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Anne-Lise Borresen-DaleDepartment of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo University Hospital, Oslo, Norway.
Thibaud S BoutinMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Hiltrud BrauchDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Thomas BrüningInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
Barbara BurwinkelDivision of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Archie CampbellMedical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Harry CampbellInstitute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
J Ross ChapmanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Yii-Der Ida ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
Georgia Chenevix-TrenchDepartment of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Andrea D CovielloBoston University School of Medicine, Department of Medicine, Sections of Preventive Medicine and Endocrinology, Boston, MA.
Angela CoxSheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
Hatef DarabiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
Immaculata De VivoDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Ellen W DemerathDivision of Epidemiology & Community Health, University of Minnesotta, Minneapolis MN 55455.
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Peter DevileeDepartment of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Thilo DörkGynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Isabel Dos-Santos-SilvaNon-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
John D EicherNHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
Peter A FaschingDepartment of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Jessica D FaulSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Jonine FigueroaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Dieter Flesch-JanysDepartment of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
Ilaria GandinInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Melissa E GarciaLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
Montserrat García-ClosasDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Graham G GilesCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Giorgia G GirottoDepartment of Clinical Medical Sciences, Surgical and Health, University of Trieste, 34149 Trieste, Italy.
Mark S GoldbergDepartment of Medicine, McGill University, Montreal, Canada.
Anna González-NeiraHuman Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Mark O GoodarziDivision of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Megan L GroveHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Daniel F GudbjartssondeCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
Pascal GuénelEnvironmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
Ute HamannMolecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lynne J HockingMusculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Albert HofmanGenetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
Maartje J HooningDepartment of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
John L HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Frank B HuDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Jinyan HuangState Key Laboratory of Medical Genomics,Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Keith HumphreysDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
David J HunterDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Anna JakubowskaDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Samuel E JonesGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Maria KabischMolecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
David KarasikHarvard Medical School, Boston, MA 02115, USA.
Julia A KnightProsserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
Ivana KolcicFaculty of Medicine, University of Split, Split, Croatia.
Charles KooperbergFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
Veli-Matti KosmaCancer Center, Kuopio University Hospital, Kuopio, Finland.
Jennifer KriebelResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Vessela KristensenDepartment of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo University Hospital, Oslo, Norway.
Diether LambrechtsVesalius Research Center (VRC), VIB, Leuven, Belgium.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Jingmei LiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
Xin LiDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Sara LindströmDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Yongmei LiuCenter for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Jan LubinskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Reedik MägiEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Arto MannermaaCancer Center, Kuopio University Hospital, Kuopio, Finland.
Judith ManzResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Sara MargolinDepartment of Oncology - Pathology, Karolinska Institutet, Stockholm 17177, Sweden.
Jonathan MartenMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Nicholas G MartinQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Corrado MasciulloDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
Alfons MeindlDivision of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
Kyriaki MichailidouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Lili MilaniEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Roger L MilneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Michael NallsLaboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
Ben M NealeStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Heli NevanlinnaDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Patrick NevenKULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, Belgium.
Anne B NewmanDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Børge G NordestgaardFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Janet E OlsonDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Sandosh PadmanabhanBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Paolo PeterlongoIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
Ulrike PetersFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
Astrid PetersmannInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
Julian PetoNon-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Nicola N PirastuInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Ailith PirieCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Giorgio PistisInstitute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
Ozren PolasekFaculty of Medicine, University of Split, Split, Croatia.
David PorteousMedical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle Washington 98101 USA.
Katri PylkäsLaboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
Paolo RadiceUnit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
Leslie J RaffelMedical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
Igor RudanInstitute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
Anja RudolphDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniela RuggieroInstitute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
Cinzia F SalaDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
Serena SannaInstitute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
Elinor J SawyerResearch Oncology, Guy's Hospital, King's College London, London, UK.
David SchlessingerNational Institute on Aging, Intramural Research Program, Baltimore, MD 20892, USA.
Marjanka K SchmidtNetherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
Frank SchmidtInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
Rita K SchmutzlerDivision of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.
Minouk J SchoemakerDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Robert A ScottMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Caroline M SeynaeveDepartment of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jacques SimardCentre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
Rossella SoriceInstitute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
Melissa C SoutheyDepartment of Pathology, The University of Melbourne, Melbourne, Australia.
Doris StöcklInstitute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Anthony SwerdlowDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
Unnur ThorsteinsdottirdeCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
Amanda E TolandDepartment of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Ian TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Thérèse TruongEnvironmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
Laufey TryggvadottirIcelandic Cancer Registry, Reykjavik, Iceland.
Stephen T TurnerDivision of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Diego VozziInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Melissa WellonsDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, 37203, USA.
Gonneke WillemsenDepartment of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
James F WilsonMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Robert WinqvistLaboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
Bruce B H R WolffenbuttelDepartment of Endocrinology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Alan F WrightMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Drakoulis YannoukakosMolecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Athens, Greece.
Tatijana ZemunikFaculty of Medicine, University of Split, Split, Croatia.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Marek ZygmuntDepartment of Obstetrics and Gynecology, University Medicine Greifswald, 17475 Greifswald, Germany.
Sven BergmannDepartment of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.
Dorret I BoomsmaDepartment of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Julie E BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21224, United States of America.
Grant W MontgomeryQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland.
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
Cornelia M van DuijnGenetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
Behrooz Z AlizadehDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Marina CiulloInstitute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
Laura CrisponiInstitute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
Paolo P GaspariniInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Peter KraftDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Barbara McKnightDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Alanna C MorrisonHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Alex P ReinerFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
Daniela TonioloDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
André G UitterlindenDepartment of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
Sheila UliviInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
David R WeirSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Laura M Yerges-ArmstrongProgram in Personalized Medicine, Division of Endocrinology, Diabetes and Nutrition - University of Maryland School of Medicine, USA. Baltimore, MD 21201.
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EPIC-InterAct Consortium
LifeLines Cohort Study
Alkes L PriceDepartment of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Kari StefanssondeCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
Jenny A VisserDepartment of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
Ken K OngMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Joanne M MurabitoNHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
John R B PerryMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Anna MurrayGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
University of Cambridge · GBGerman Cancer Research Center · DEBrigham and Women's Hospital · USHarvard University · USUniversity of Michigan · USBroad Institute · USUniversitätsmedizin Greifswald · DEUniversity of Trieste · ITdeCODE Genetics (Iceland) · ISHelmholtz Zentrum München · DEBoston University · USInstitute of Cancer Research · GBKarolinska Institutet · SEUniversity Medical Center Groningen · NLUniversity of Exeter · GBCedars-Sinai Medical Center · USOslo University Hospital · NOSIB Swiss Institute of Bioinformatics · CHThe University of Melbourne · AUUniversité Paris-Sud · FR

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Hormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
Core-001U01CA164920 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Irene Andrulis, Sarah Violet Colonna · 2018 to 2026
$17.0M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 11174Cancer Research UK 15007Cancer Research UK 16459Cancer Research UK 16561Cancer Research UK 16563Cancer Research UK 16565Cancer Research UK 17528Cancer Research UK C12292/A11174Cancer Research UK C1281/A12014Cancer Research UK C1287/A10118Cancer Research UK C1287/A 10710Cancer Research UK C5047/A10692Cancer Research UK C5047/A15007Cancer Research UK C5047/A8384Cancer Research UK C8197/A16565Chief Scientist Office CZD/16/6/4Medical Research Council MC_PC_U127561128Medical Research Council MC_U106179471Medical Research Council MC_U106179472Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/2NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCATS NIH HHS UL1 TR001108NCI NIH HHS 1U19 CA148065NCI NIH HHS 1U19 CA148112NCI NIH HHS 1U19 CA148537NCI NIH HHS CA128978NCI NIH HHS CA164920NCI NIH HHS P30 CA015704NCI NIH HHS UM1 CA182910NCI NIH HHS UM1 CA182913NCRR NIH HHS UL1RR025005NHGRI NIH HHS HG005552NHGRI NIH HHS HG005581NHGRI NIH HHS HG006513NHGRI NIH HHS HG007022NHGRI NIH HHS HG007089NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01HG004402NHLBI NIH HHS 5RC2HL102419NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201100046CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL043851NHLBI NIH HHS HL054457NHLBI NIH HHS HL054464NHLBI NIH HHS HL054481NHLBI NIH HHS HL080295NHLBI NIH HHS HL080467NHLBI NIH HHS HL087652NHLBI NIH HHS HL087660NHLBI NIH HHS HL105756NHLBI NIH HHS K01-HL116770NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N02-HL-6-4278NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087660NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01HL59367NHLBI NIH HHS U01-HL72515NHLBI NIH HHS U01-HL84756NIA NIH HHS 1R01AG032098-01A1NIA NIH HHS AG009740NIA NIH HHS AG023629NIA NIH HHS HHSN271201100004CNIA NIH HHS N01-AG-1-2109NIA NIH HHS N01-AG-5-0002NIA NIH HHS N01AG62101NIA NIH HHS N01AG62103NIA NIH HHS N01AG62106NIA NIH HHS N.1-AG-1-1NIA NIH HHS N.1-AG-1-2111NIA NIH HHS R01AG29451NIA NIH HHS R21 AG032598NIA NIH HHS R21AG032598NIA NIH HHS RC2 AG036495NIA NIH HHS RC4 AG039029NIA NIH HHS U01 AG009740NIA NIH HHS U01AG009740NIDA NIH HHS HHSN271201100005CNIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488NIDDK NIH HHS P30-DK072488NIDDK NIH HHS R01DK075787Wellcome Trust 090532WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
6 · The paper itself

Abstract

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Indexed as

DNA RepairAdultAge FactorsAgingBRCA1 ProteinBreast NeoplasmsFemaleGene Regulatory NetworksGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenomicsGenotypeHumansHypothalamusMenopauseBRCA1 Protein

Identifiers

PMID26414677
PMCPMC4661791
OpenAlexW1904407543

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.