Journal article

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

  • Day FR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Ruth KS Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
  • Thompson DJ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Lunetta KL Boston University School of Public Health, Department of Biostatistics. Boston, Massachusetts 02118, USA.
  • Pervjakova N Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Chasman DI Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
  • Stolk L Department of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
  • Finucane HK Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Sulem P deCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
  • Bulik-Sullivan B Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Esko T Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Johnson AD NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
  • Elks CE MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Franceschini N Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • He C Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN 46202, USA.
  • Altmaier E Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Brody JA Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle Washington 98101 USA.
  • Franke LL Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Huffman JE NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
  • Keller MF Merck Pharmaceuticals, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
  • McArdle PF Program in Personalized Medicine, Division of Endocrinology, Diabetes and Nutrition - University of Maryland School of Medicine, USA. Baltimore, MD 21201.
  • Nutile T Institute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
  • Porcu E Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
  • Robino A Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Rose LM Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
  • Schick UM Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
  • Smith JA Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Teumer A Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Traglia M Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Vuckovic D Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Yao J The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Zhao W Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Albrecht E Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Amin N Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
  • Corre T Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.
  • Hottenga JJ Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
  • Mangino M Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
  • Smith AV Icelandic Heart Association, Kopavogur, Iceland.
  • Tanaka T Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21224, United States of America.
  • Abecasis G Center for Statistical Genetics, Ann Arbor, University of Michigan, Michigan 48109-2029, USA.
  • Andrulis IL Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
  • Anton-Culver H Department of Epidemiology, University of California Irvine, Irvine, California, USA.
  • Antoniou AC Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Arndt V Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Arnold AM Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Barbieri C Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Beckmann MW Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Beeghly-Fadiel A Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Benitez J Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Bernstein L Beckman Research Institute of City of Hope, Duarte, CA, USA.
  • Bielinski SJ Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
  • Blomqvist C Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
  • Boerwinkle E Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Bogdanova NV Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
  • Bojesen SE Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Bolla MK Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Borresen-Dale AL Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo University Hospital, Oslo, Norway.
  • Boutin TS Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Brauch H Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
  • Brenner H Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Brüning T Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany.
  • Burwinkel B Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Campbell A Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Campbell H Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
  • Chanock SJ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Chapman JR Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Chen YI The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Chenevix-Trench G Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Couch FJ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Coviello AD Boston University School of Medicine, Department of Medicine, Sections of Preventive Medicine and Endocrinology, Boston, MA.
  • Cox A Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.
  • Czene K Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • Darabi H Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • De Vivo I Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Demerath EW Division of Epidemiology & Community Health, University of Minnesotta, Minneapolis MN 55455.
  • Dennis J Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Devilee P Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
  • Dörk T Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Dos-Santos-Silva I Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
  • Dunning AM Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Eicher JD NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
  • Fasching PA Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Faul JD Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Figueroa J Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Flesch-Janys D Department of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
  • Gandin I Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Garcia ME Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
  • García-Closas M Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Giles GG Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Girotto GG Department of Clinical Medical Sciences, Surgical and Health, University of Trieste, 34149 Trieste, Italy.
  • Goldberg MS Department of Medicine, McGill University, Montreal, Canada.
  • González-Neira A Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Goodarzi MO Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Grove ML Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Gudbjartsson DF deCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
  • Guénel P Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
  • Guo X The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Haiman CA Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Hall P Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • Hamann U Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
  • Henderson BE Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Hocking LJ Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen AB25 2ZD, UK.
  • Hofman A Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
  • Homuth G Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Hooning MJ Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Hopper JL Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Hu FB Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Huang J State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Humphreys K Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • Hunter DJ Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Jakubowska A Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Jones SE Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
  • Kabisch M Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
  • Karasik D Harvard Medical School, Boston, MA 02115, USA.
  • Knight JA Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
  • Kolcic I Faculty of Medicine, University of Split, Split, Croatia.
  • Kooperberg C Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
  • Kosma VM Cancer Center, Kuopio University Hospital, Kuopio, Finland.
  • Kriebel J Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Kristensen V Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo University Hospital, Oslo, Norway.
  • Lambrechts D Vesalius Research Center (VRC), VIB, Leuven, Belgium.
  • Langenberg C MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Li J Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • Li X Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Lindström S Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • Liu Y Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine.
  • Luan J MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Lubinski J Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Mägi R Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Mannermaa A Cancer Center, Kuopio University Hospital, Kuopio, Finland.
  • Manz J Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Margolin S Department of Oncology - Pathology, Karolinska Institutet, Stockholm 17177, Sweden.
  • Marten J Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Martin NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Masciullo C Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Meindl A Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
  • Michailidou K Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Mihailov E Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Milani L Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Milne RL Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Müller-Nurasyid M Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Nalls M Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
  • Neale BM Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Nevanlinna H Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
  • Neven P KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, Belgium.
  • Newman AB Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Nordestgaard BG Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Olson JE Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
  • Padmanabhan S British 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.
  • Peterlongo P IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
  • Peters U Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
  • Petersmann A Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Peto J Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
  • Pharoah PDP Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Pirastu NN Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Pirie A Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Pistis G Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
  • Polasek O Faculty of Medicine, University of Split, Split, Croatia.
  • Porteous D Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Psaty BM Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle Washington 98101 USA.
  • Pylkäs K Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
  • Radice P Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
  • Raffel LJ Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Rivadeneira F Department of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
  • Rudan I Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
  • Rudolph A Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Ruggiero D Institute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
  • Sala CF Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Sanna S Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
  • Sawyer EJ Research Oncology, Guy's Hospital, King's College London, London, UK.
  • Schlessinger D National Institute on Aging, Intramural Research Program, Baltimore, MD 20892, USA.
  • Schmidt MK Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
  • Schmidt F Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Schmutzler RK Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.
  • Schoemaker MJ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Scott RA MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Seynaeve CM Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Simard J Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
  • Sorice R Institute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
  • Southey MC Department of Pathology, The University of Melbourne, Melbourne, Australia.
  • Stöckl D Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Strauch K Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Swerdlow A Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Taylor KD The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Thorsteinsdottir U deCODE genetics/Amgen, Inc., IS-101 Reykjavik, Iceland.
  • Toland AE Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • Tomlinson I Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Truong T Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
  • Tryggvadottir L Icelandic Cancer Registry, Reykjavik, Iceland.
  • Turner ST Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
  • Vozzi D Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Wang Q Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Wellons M Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, 37203, USA.
  • Willemsen G Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
  • Wilson JF Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Winqvist R Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.
  • Wolffenbuttel BBHR Department of Endocrinology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Wright AF Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Yannoukakos D Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Athens, Greece.
  • Zemunik T Faculty of Medicine, University of Split, Split, Croatia.
  • Zheng W Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Zygmunt M Department of Obstetrics and Gynecology, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Bergmann S Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.
  • Boomsma DI Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
  • Buring JE Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
  • Ferrucci L Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21224, United States of America.
  • Montgomery GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Gudnason V Icelandic Heart Association, Kopavogur, Iceland.
  • Spector TD Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
  • van Duijn CM Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands.
  • Alizadeh BZ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Ciullo M Institute of Genetics and Biophysics - CNR, via Pietro Castellino 111, 80131, Naples, Italy.
  • Crisponi L Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy.
  • Easton DF Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, UK.
  • Gasparini PP Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Gieger C Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Harris TB Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
  • Hayward C Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Kardia SLR Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Kraft P Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • McKnight B Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Metspalu A Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Morrison AC Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Reiner AP Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109-1024, USA.
  • Ridker PM Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
  • Rotter JI The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Toniolo D Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Uitterlinden AG Department of Internal Medicine, Erasmus MC, 3015GE Rotterdam, the Netherlands.
  • Ulivi S Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
  • Völzke H Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
  • Wareham NJ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Weir DR Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Yerges-Armstrong LM Program in Personalized Medicine, Division of Endocrinology, Diabetes and Nutrition - University of Maryland School of Medicine, USA. Baltimore, MD 21201.
  • Price AL MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Stefansson K Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
  • Visser JA
  • Ong KK
  • Chang-Claude J
  • Murabito JM
  • Perry JRB
  • Murray A
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  • 2015-09-29
Published in:
  • Nature genetics. - 2015
English 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.
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  • English
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https://folia.unifr.ch/global/documents/100058
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