Publication Date:
2014-09-19
Description:
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P 〈 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185210/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, John R B -- Day, Felix -- Elks, Cathy E -- Sulem, Patrick -- Thompson, Deborah J -- Ferreira, Teresa -- He, Chunyan -- Chasman, Daniel I -- Esko, Tonu -- Thorleifsson, Gudmar -- Albrecht, Eva -- Ang, Wei Q -- Corre, Tanguy -- Cousminer, Diana L -- Feenstra, Bjarke -- Franceschini, Nora -- Ganna, Andrea -- Johnson, Andrew D -- Kjellqvist, Sanela -- Lunetta, Kathryn L -- McMahon, George -- Nolte, Ilja M -- Paternoster, Lavinia -- Porcu, Eleonora -- Smith, Albert V -- Stolk, Lisette -- Teumer, Alexander -- Tsernikova, Natalia -- Tikkanen, Emmi -- Ulivi, Sheila -- Wagner, Erin K -- Amin, Najaf -- Bierut, Laura J -- Byrne, Enda M -- Hottenga, Jouke-Jan -- Koller, Daniel L -- Mangino, Massimo -- Pers, Tune H -- Yerges-Armstrong, Laura M -- Hua Zhao, Jing -- Andrulis, Irene L -- Anton-Culver, Hoda -- Atsma, Femke -- Bandinelli, Stefania -- Beckmann, Matthias W -- Benitez, Javier -- Blomqvist, Carl -- Bojesen, Stig E -- Bolla, Manjeet K -- Bonanni, Bernardo -- Brauch, Hiltrud -- Brenner, Hermann -- Buring, Julie E -- Chang-Claude, Jenny -- Chanock, Stephen -- Chen, Jinhui -- Chenevix-Trench, Georgia -- Collee, J Margriet -- Couch, Fergus J -- Couper, David -- Coviello, Andrea D -- Cox, Angela -- Czene, Kamila -- D'adamo, Adamo Pio -- Davey Smith, George -- De Vivo, Immaculata -- Demerath, Ellen W -- Dennis, Joe -- Devilee, Peter -- Dieffenbach, Aida K -- Dunning, Alison M -- Eiriksdottir, Gudny -- Eriksson, Johan G -- Fasching, Peter A -- Ferrucci, Luigi -- Flesch-Janys, Dieter -- Flyger, Henrik -- Foroud, Tatiana -- Franke, Lude -- Garcia, Melissa E -- Garcia-Closas, Montserrat -- Geller, Frank -- de Geus, Eco E J -- Giles, Graham G -- Gudbjartsson, Daniel F -- Gudnason, Vilmundur -- Guenel, Pascal -- Guo, Suiqun -- Hall, Per -- Hamann, Ute -- Haring, Robin -- Hartman, Catharina A -- Heath, Andrew C -- Hofman, Albert -- Hooning, Maartje J -- Hopper, John L -- Hu, Frank B -- Hunter, David J -- Karasik, David -- Kiel, Douglas P -- Knight, Julia A -- Kosma, Veli-Matti -- Kutalik, Zoltan -- Lai, Sandra -- Lambrechts, Diether -- Lindblom, Annika -- Magi, Reedik -- Magnusson, Patrik K -- Mannermaa, Arto -- Martin, Nicholas G -- Masson, Gisli -- McArdle, Patrick F -- McArdle, Wendy L -- Melbye, Mads -- Michailidou, Kyriaki -- Mihailov, Evelin -- Milani, Lili -- Milne, Roger L -- Nevanlinna, Heli -- Neven, Patrick -- Nohr, Ellen A -- Oldehinkel, Albertine J -- Oostra, Ben A -- Palotie, Aarno -- Peacock, Munro -- Pedersen, Nancy L -- Peterlongo, Paolo -- Peto, Julian -- Pharoah, Paul D P -- Postma, Dirkje S -- Pouta, Anneli -- Pylkas, Katri -- Radice, Paolo -- Ring, Susan -- Rivadeneira, Fernando -- Robino, Antonietta -- Rose, Lynda M -- Rudolph, Anja -- Salomaa, Veikko -- Sanna, Serena -- Schlessinger, David -- Schmidt, Marjanka K -- Southey, Mellissa C -- Sovio, Ulla -- Stampfer, Meir J -- Stockl, Doris -- Storniolo, Anna M -- Timpson, Nicholas J -- Tyrer, Jonathan -- Visser, Jenny A -- Vollenweider, Peter -- Volzke, Henry -- Waeber, Gerard -- Waldenberger, Melanie -- Wallaschofski, Henri -- Wang, Qin -- Willemsen, Gonneke -- Winqvist, Robert -- Wolffenbuttel, Bruce H R -- Wright, Margaret J -- Australian Ovarian Cancer Study -- GENICA Network -- kConFab -- LifeLines Cohort Study -- InterAct Consortium -- Early Growth Genetics (EGG) Consortium -- Boomsma, Dorret I -- Econs, Michael J -- Khaw, Kay-Tee -- Loos, Ruth J F -- McCarthy, Mark I -- Montgomery, Grant W -- Rice, John P -- Streeten, Elizabeth A -- Thorsteinsdottir, Unnur -- van Duijn, Cornelia M -- Alizadeh, Behrooz Z -- Bergmann, Sven -- Boerwinkle, Eric -- Boyd, Heather A -- Crisponi, Laura -- Gasparini, Paolo -- Gieger, Christian -- Harris, Tamara B -- Ingelsson, Erik -- Jarvelin, Marjo-Riitta -- Kraft, Peter -- Lawlor, Debbie -- Metspalu, Andres -- Pennell, Craig E -- Ridker, Paul M -- Snieder, Harold -- Sorensen, Thorkild I A -- Spector, Tim D -- Strachan, David P -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Widen, Elisabeth -- Zygmunt, Marek -- Murray, Anna -- Easton, Douglas F -- Stefansson, Kari -- Murabito, Joanne M -- Ong, Ken K -- 098381/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179472/Medical Research Council/United Kingdom -- MC_UU_12013/1/Medical Research Council/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MR/J012165/1/Medical Research Council/United Kingdom -- P50 CA116201/CA/NCI NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):92-7. doi: 10.1038/nature13545. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [4] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [5]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2]. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2]. ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Department of Epidemiology, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana 46202, USA. [2] Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [3] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [4] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; School of Women's and Infants' Health, The University of Western Australia, WA-6009, Australia. ; 1] Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland. [2] Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. ; Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden. ; NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. ; Science for Life Laboratory, Karolinska Institutet, Stockholm, Box 1031, 17121 Solna, Sweden. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Public Health, Department of Biostatistics, Boston, Massachusetts 02118, USA. ; 1] MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. [2] School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; 1] Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. [2] University of Sassari, Department of Biomedical Sciences, 07100 Sassari, Italy. ; 1] Icelandic Heart Association, IS-201 Kopavogur, Iceland. [2] University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Department of Biotechnology, University of Tartu, 51010 Tartu, Estonia. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Hjelt Institute, University of Helsinki, FI-00014, Finland. ; Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. ; Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. ; Department of Psychiatry, Washington University, St Louis, Missouri 63110, USA. ; 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland 4072, Australia. [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [3] Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical 142 University of Denmark, DK-2800 Lyngby, Denmark. ; Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Epidemiology, University of California Irvine, Irvine, California 92697-7550, USA. ; Sanquin Research, 6525 GA Nijmegen, The Netherlands. ; 1] Tuscany Regional Health Agency, Florence, Italy, I.O.T. and Department of Medical and Surgical Critical Care, University of Florence, 50134 Florence, Italy. [2] Geriatric Unit, Azienda Sanitaria di Firenze, 50122 Florence, Italy. ; University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, D-91054 Erlangen, Germany. ; 1] Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain. [2] Centro de Investigacion en Red de Enfermedades Raras (CIBERER), E-46010 Valencia, Spain. ; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00100 Helsinki, Finland. ; 1] Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. [2] Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. ; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), 20139 Milan, Italy. ; 1] DrMargarete Fischer-Bosch-Institute of Clinical Pharmacology, D-70376 Stuttgart, Germany. [2] University of Tubingen, D-72074 Tubingen, Germany. ; 1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. [2] German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. ; 1] Departments of Anatomy and Neurological Surgery, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. [2] Stark Neuroscience Research Center, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006 Australia. ; Department of Clinical Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands. ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7420, USA. ; Boston University School of Medicine, Department of Medicine, Sections of Preventive Medicine and Endocrinology, Boston, Massachusetts 02118, USA. ; Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK. ; 1] Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. [2] Department of Clinical Medical Sciences, Surgical and Health, University of Trieste, 34149 Trieste, Italy. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Department of Human Genetics &Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge CB1 8RN, UK. ; Icelandic Heart Association, IS-201 Kopavogur, Iceland. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary health Care, University of Helsinki, FI-00014 Helsinki, Finland. [3] Helsinki University Central Hospital, Unit of General Practice, FI-00029 HUS Helsinki, Finland. [4] Folkhalsan Research Centre, FI-00290 Helsinki, Finland. ; Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 20892, USA. ; Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, D-20246 Hamburg, Germany. ; Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark. ; Department of Genetics, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; National Insitute on Aging, National Institutes of Health, Baltimore, Maryland 20892, USA. ; 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. [2] Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London SW3 6JB, UK. ; 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. [2] EMGO + Institute for Health and Care Research, VU University Medical Centre, Van der Boechorststraat 7, 1081 Bt, Amsterdam, The Netherlands. ; 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, F-94807 Villejuif, France. [2] University Paris-Sud, UMRS 1018, F-94807 Villejuif, France. ; Department of Obstetrics and Gynecology, Southern Medical University, 510515 Guangzhou, China. ; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Washington University, Department of Psychiatry, St Louis, Missouri 63110, USA. ; Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Department of Medical Oncology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. ; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. ; 1] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. [2] Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. ; 1] School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. [2] Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, P.O. Box 100, FI-70029 Kuopio, Finland. ; Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. ; 1] Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. ; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. ; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. ; School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; 1] Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. [2] Department of Medicine, Stanford School of Medicine, Stanford, California 94305-5101, USA. ; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, P.O. Box 100, FI-00029 HUS Helsinki, Finland. ; KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, 3000 Leuven, Belgium. ; Research Unit of Obstetrics &Gynecology, Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark. ; Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy. ; Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. ; University Groningen, University Medical Center Groningen, Department Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, P.O. Box 30.001, NL-9700 RB Groningen, The Netherlands. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of Obstetrics and Gynecology, Oulu University Hospital, P.O. Box 10, FI-90029 OYS Oulu, Finland. ; Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital/NordLab Oulu, P.O. Box 3000, FI-90014 Oulu, Finland. ; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [3] Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. ; National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224-6825, USA. ; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Postbus 90203, 1006 BE Amsterdam, The Netherlands. ; Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, UK. ; 1] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. [2] Department of Obstetrics and Gynaecology, Campus Grosshadern, Ludwig-Maximilians-University, D-81377 Munich, Germany. ; Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. ; Department of Internal Medicine, Lausanne University Hospital, CH-1015 Lausanne, Switzerland. ; 1] Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. ; 1] Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Endocrinology, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Queensland Insitute of Medical Research, Brisbane, Queensland 4029, Australia. ; 1] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. [2] Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0QQ, UK. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, Box 1003, New York, New York 10029, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LE, UK. [3] Oxford Centre for Diabetes, Endocrinology, &Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. ; 1] Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Geriatric Research and Education Clinical Center (GRECC) - Veterans Administration Medical Center, Baltimore, Maryland 21201, USA. ; 1] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [2] Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. [3] Centre of Medical Systems Biology, PO Box 9600, 2300 RC Leiden, the Netherlands. ; Human Genetics Center and Divof Epidemiology, University of Houston, P.O. Box 20186, Texas 77025 USA. ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Box 256, 751 05 Uppsala, Sweden. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Institute of Health Sciences, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland. [3] Biocenter Oulu, University of Oulu, P.O. Box 5000, Aapistie 5A, FI-90014 Oulu, Finland. [4] Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland. [5] Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220 Oulu, 90029 OYS, Finland. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Denmark. [2] Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, DK-2000 Frederiksberg, Denmark. ; Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. ; Department of Obstetrics and Gynecology, University Medicine Greifswald, D-17475 Greifswald, Germany. ; University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. [3]. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, Massachusetts 02118, USA. [3]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK. [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231870" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Age Factors
;
*Alleles
;
Body Mass Index
;
Breast Neoplasms/genetics
;
Cardiovascular Diseases/genetics
;
Child
;
Diabetes Mellitus, Type 2/genetics
;
Europe/ethnology
;
Female
;
Genetic Loci/*genetics
;
Genome-Wide Association Study
;
Genomic Imprinting/genetics
;
Humans
;
Hypothalamo-Hypophyseal System/physiology
;
Intercellular Signaling Peptides and Proteins/genetics
;
Male
;
Membrane Proteins/genetics
;
Menarche/*genetics
;
Obesity/genetics
;
Ovary/physiology
;
*Parents
;
Polymorphism, Single Nucleotide/genetics
;
Potassium Channels, Tandem Pore Domain/genetics
;
Proteins/genetics
;
Quantitative Trait Loci/genetics
;
Receptors, GABA-B/metabolism
;
Receptors, Retinoic Acid/metabolism
;
Ribonucleoproteins/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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