Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (original) (raw)
References
- Parent, A.S. et al. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr. Rev. 24, 668–693 (2003).
Article PubMed Google Scholar - Kvale, G. Reproductive factors in breast cancer epidemiology. Acta Oncol. 31, 187–194 (1992).
Article CAS PubMed Google Scholar - Purdie, D.M. & Green, A.C. Epidemiology of endometrial cancer. Best Pract. Res. Clin. Obstet. Gynaecol. 15, 341–354 (2001).
Article CAS PubMed Google Scholar - Ong, K.K. et al. Earlier mother's age at menarche predicts rapid infancy growth and childhood obesity. PLoS Med. 4, e132 (2007).
Article PubMed PubMed Central Google Scholar - He, C. et al. Age at menarche and risk of type 2 diabetes: results from 2 large prospective cohort studies. Am. J. Epidemiol. 171, 334–344 (2010).
Article PubMed Google Scholar - Lakshman, R. et al. Early age at menarche associated with cardiovascular disease and mortality. J. Clin. Endocrinol. Metab. 94, 4953–4960 (2009).
Article CAS PubMed Google Scholar - Towne, B. et al. Heritability of age at menarche in girls from the Fels Longitudinal Study. Am. J. Phys. Anthropol. 128, 210–219 (2005).
Article PubMed Google Scholar - He, C. et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat. Genet. 41, 724–728 (2009).
Article CAS PubMed PubMed Central Google Scholar - Ong, K.K. et al. Genetic variation in LIN28B is associated with the timing of puberty. Nat. Genet. 41, 729–733 (2009).
Article CAS PubMed PubMed Central Google Scholar - Perry, J.R. et al. Meta-analysis of genome-wide association data identifies two loci influencing age at menarche. Nat. Genet. 41, 648–650 (2009).
Article CAS PubMed PubMed Central Google Scholar - Sulem, P. et al. Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche. Nat. Genet. 41, 734–738 (2009).
Article CAS PubMed Google Scholar - Raivio, T. & Dunkel, L. Inhibins in childhood and puberty. Best Pract. Res. Clin. Endocrinol. Metab. 16, 43–52 (2002).
Article CAS PubMed Google Scholar - Crofton, P.M. et al. Changes in dimeric inhibin A and B during normal early puberty in boys and girls. Clin. Endocrinol. 46, 109–114 (1997).
Article CAS Google Scholar - Sehested, A. et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. J. Clin. Endocrinol. Metab. 85, 1634–1640 (2000).
CAS PubMed Google Scholar - Burger, H.G. Evidence for a negative feedback role of inhibin in follicle stimulating hormone regulation in women. Hum. Reprod. 8 (Suppl 2), 129–132 (1993).
Article CAS PubMed Google Scholar - Sulzbacher, S., Schroeder, I.S., Truong, T.T. & Wobus, A.M. Activin A-induced differentiation of embryonic stem cells into endoderm and pancreatic progenitors—the influence of differentiation factors and culture conditions. Stem Cell Rev. 5, 159–173 (2009).
Article CAS Google Scholar - Dolle, P. Developmental expression of retinoic acid receptors (RARs). Nucl. Recept. Signal. 7, e006 (2009).
Article PubMed PubMed Central Google Scholar - Frayling, T.M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007).
Article CAS PubMed PubMed Central Google Scholar - Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 41, 18–24 (2009).
Article CAS PubMed Google Scholar - Willer, C.J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41, 25–34 (2009).
Article CAS PubMed Google Scholar - Sakkou, M. et al. A role for brain-specific homeobox factor Bsx in the control of hyperphagia and locomotory behavior. Cell Metab. 5, 450–463 (2007).
Article CAS PubMed Google Scholar - Altarejos, J.Y. et al. The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nat. Med. 14, 1112–1117 (2008).
Article CAS PubMed PubMed Central Google Scholar - Pissios, P., Bradley, R.L. & Maratos-Flier, E. Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions. Endocr. Rev. 27, 606–620 (2006).
Article CAS PubMed Google Scholar - Wu, M., Dumalska, I., Morozova, E., van den Pol, A. & Alreja, M. Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction. Proc. Natl. Acad. Sci. USA 106, 17217–17222 (2009).
Article CAS PubMed PubMed Central Google Scholar - Conrad, D.F. et al. Origins and functional impact of copy number variation in the human genome. Nature 464, 704–712 (2009).
Article PubMed PubMed Central Google Scholar - Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008).
Article CAS PubMed Google Scholar - Kernie, S.G., Liebl, D.J. & Parada, L.F. BDNF regulates eating behavior and locomotor activity in mice. EMBO J. 19, 1290–1300 (2000).
Article CAS PubMed PubMed Central Google Scholar - Xu, B. et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci. 6, 736–742 (2003).
Article CAS PubMed PubMed Central Google Scholar - Temple, I.K., Shrubb, V., Lever, M., Bullman, H. & Mackay, D.J. Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14. J. Med. Genet. 44, 637–640 (2007).
Article CAS PubMed PubMed Central Google Scholar - Drouin, J., Lamolet, B., Lamonerie, T., Lanctot, C. & Tremblay, J.J. The PTX family of homeodomain transcription factors during pituitary developments. Mol. Cell. Endocrinol. 140, 31–36 (1998).
Article CAS PubMed Google Scholar - Topaloglu, A.K. et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat. Genet. 41, 354–358 (2009).
Article CAS PubMed Google Scholar - Gajdos, Z.K. et al. Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche. J. Clin. Endocrinol. Metab. 93, 4290–4298 (2008).
Article CAS PubMed PubMed Central Google Scholar - Stavrou, I., Zois, C., Ioannidis, J.P. & Tsatsoulis, A. Association of polymorphisms of the oestrogen receptor alpha gene with the age of menarche. Hum. Reprod. 17, 1101–1105 (2002).
Article CAS PubMed Google Scholar - Kaprio, J. et al. Common genetic influences on BMI and age at menarche. Hum. Biol. 67, 739–753 (1995).
CAS PubMed Google Scholar - Onland-Moret, N.C. et al. Age at menarche in relation to adult height: the EPIC study. Am. J. Epidemiol. 162, 623–632 (2005).
Article CAS PubMed Google Scholar - Welt, C.K. et al. Recombinant human leptin in women with hypothalamic amenorrhea. N. Engl. J. Med. 351, 987–997 (2004).
Article CAS PubMed Google Scholar - Pocai, A. et al. Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. J. Clin. Invest. 116, 1081–1091 (2006).
Article CAS PubMed PubMed Central Google Scholar - Devlin, B., Bacanu, S.A. & Roeder, K. Genomic Control to the extreme. Nat. Genet. 36, 1129–1130 author reply 1131 (2004).
Article CAS PubMed Google Scholar - Manolio, T.A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).
Article CAS PubMed PubMed Central Google Scholar - Must, A. et al. Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember? Am. J. Epidemiol. 155, 672–679 (2002).
Article CAS PubMed Google Scholar - Widén, E. et al. Distinct variants at LIN28B influence growth in height from birth to adulthood. Am. J. Hum. Genet. 86, 773–782 (2010).
Article PubMed PubMed Central Google Scholar - Herman-Giddens, M.E. et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 99, 505–512 (1997).
Article CAS PubMed Google Scholar - Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).
Article CAS PubMed Google Scholar - Segrè, A.V. et al. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).
Article PubMed PubMed Central Google Scholar
Acknowledgements
Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics 129680, 120315, 129287, 129494); Affymetrix (N02-HL-6-4278); Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association (0855082E); Amgen; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667); Australian Research Council (A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096); Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research (grant ID 166067); Cancer Research United Kingdom; the Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); the Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland (P30 DK072488); Danish National Research Foundation; Danish Pharmacists' Fund; the Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (SF0180142s08); the European Commision (212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865 - GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, GenomEUtwin Project QLG2-CT-2002-01254, EU/QLRT-2001-01254; ERC-230374); European Union framework program 6 EUROSPAN project (LSHG-CT-2006-018947, LSHM-CT-2003-503041); European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study (N01-HC-25195); GENEVA Coordinating Center (U01HG004446); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum München-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health (ICS110.1/RF97.71, RF-FSR-2007-647201); Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; the Medical Research Council (G0000934, G0500539, G0701863); National Cancer Institute (CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021); Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia (572613 and 003209); National Heart, Lung, and Blood Institute (HL 043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419); National Human Genome Research Institute (NHGRI); National Institute of Aging (263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, Genetics of Reproductive Life Period and Health Outcomes - R21AG032598); National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) R01 AR/AG 41398); National Institute of Child Health and Human Development (HD-061437); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845, U01 DK062418); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HG004446, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004402, U01HG004446, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C); the National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research (904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015); Netherlands Genomic Initiative (NGI, 050-060-810), National Institute on Aging (NIA) Intramural Research Program; and Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302); Robert Dawson Evans Endowment; the Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments).
Author information
Author notes
- Leena Peltonen and Ken K Ong: Deceased.
- Cathy E Elks, John R B Perry and Patrick Sulem: These authors contributed equally to this work.
- Joanne M Murabito, Ken K Ong and Anna Murray: These senior authors jointly supervised this work.
Authors and Affiliations
- Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
Cathy E Elks, Jing Hua Zhao, Tuomas O Kilpeläinen, Shengxu Li, Nicholas J Wareham, Ruth J F Loos & Ken K Ong - Genetics of Complex Traits, Peninsula Medical School, University of Exeter, UK
John R B Perry, Michael N Weedon & Anna Murray - deCODE Genetics, Reykjavik, Iceland
Patrick Sulem, Daniel F Gudbjartsson, Thorunn Rafnar, Kari Stefansson & Unnur Thorsteinsdottir - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
Daniel I Chasman, Julie E Buring, Guillaume Paré & Paul M Ridker - Harvard Medical School, Boston, Massachusetts, USA
Daniel I Chasman, Julie E Buring, Guillaume Paré & Paul M Ridker - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Nora Franceschini - Department of Public Health, Indiana University School of Medicine, Indiana, USA
Chunyan He - Melvin and Bren Simon Cancer Center, Indiana University, Indiana, USA
Chunyan He - The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA
Kathryn L Lunetta, Andrew D Johnson, Daniel Levy & Joanne M Murabito - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
Kathryn L Lunetta & Wei Vivian Zhuang - Department of Internal Medicine, Erasmus Medical Center (MC), Rotterdam, The Netherlands
Jenny A Visser, Lisette Stolk, Fernando Rivadeneira, Joyce B J van Meurs & André G Uitterlinden - Queensland Statistical Genetics, Queensland Institute of Medical Research, Brisbane, Australia
Enda M Byrne - The University of Queensland, Brisbane, Australia
Enda M Byrne - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
Diana L Cousminer, Aarno Palotie, Leena Peltonen, Emmi Tikkanen & Elisabeth Widen - Estonian Genome Center, University of Tartu, Tartu, Estonia
Tõnu Esko, Helen Alavere, Mari Nelis, Mar-Liis Tammesoo & Andres Metspalu - Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
Tõnu Esko, Mari Nelis & Andres Metspalu - Genotyping Core Facility, Estonian Biocenter, Tartu, Estonia
Tõnu Esko, Mari Nelis & Andres Metspalu - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Bjarke Feenstra, Frank Geller, Mads Melbye & Heather A Boyd - Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands
Jouke-Jan Hottenga, Eco J C de Geus, Gonneke Willemsen & Dorret I Boomsma - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.,
Daniel L Koller, Tatiana Foroud & Michael J Econs - Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
Zoltán Kutalik & Sven Bergmann - Swiss Institute of Bioinformatics, Lausanne, Switzerland
Zoltán Kutalik & Sven Bergmann - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.,
Peng Lin, John P Rice & Laura J Bierut - Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
Massimo Mangino, Nicole Soranzo, Guangju Zhai & Tim D Spector - Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy
Mara Marongiu, Fabio Busonero, Liana Ferreli, Eleonora Porcu, Serena Sanna, Angelo Scuteri, Manuela Uda & Laura Crisponi - Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA
Patrick F McArdle, Alan R Shuldiner & Elizabeth A Streeten - Icelandic Heart Association, Kopavogur, Iceland
Albert V Smith, Thor Aspelund, Gudny Eiriksdottir & Vilmundur Gudnason - University of Iceland, Reykjavik, Iceland
Albert V Smith, Thor Aspelund & Vilmundur Gudnason - Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands
Lisette Stolk, Albert Hofman, Fernando Rivadeneira, Joyce B J van Meurs, Cornelia M van Duijn & André G Uitterlinden - Department of Epidemiology, Genetic-Epidemiology Unit, Erasmus University Medical Center, Rotterdam, The Netherlands
Sophie H van Wingerden, Najaf Amin, Ben A Oostra & Cornelia M van Duijn - Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
Eva Albrecht, Angela Döring, Christian Gieger, Thomas Illig & H Erich Wichmann - Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
Tanguy Corre, Cinzia Sala & Daniela Toniolo - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Erik Ingelsson, Patrik K E Magnusson, Per Hall & Nancy L Pedersen - MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
Caroline Hayward, Pau Navarro & Alan F Wright - Scripps Genomic Medicine, La Jolla, California, USA
Erin N Smith, Sarah S Murray & Nicholas J Schork - The Scripps Translational Science Institute, La Jolla, California, USA
Erin N Smith, Sarah S Murray & Nicholas J Schork - The Scripps Research Institute, La Jolla, California, USA
Erin N Smith, Sarah S Murray & Nicholas J Schork - Department of Reproductive Sciences and Development, Medical Genetics, University of Trieste, Trieste, Italy
Shelia Ulivi, Pio d'Adamo & Paolo Gasparini - Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, Australia
Nicole M Warrington & Lyle J Palmer - Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, Scotland
Lina Zgaga, Harry Campbell, Igor Rudan & James F Wilson - Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy
Stefania Bandinelli - Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Inês Barroso, Hannah Blackburn, Panos Deloukas, Aarno Palotie, Leena Peltonen & Nicole Soranzo - Tulane University, New Orleans, Louisiana, USA
Gerald S Berenson, Wei Chen & Sathanur R Srinivasan - Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA
Eric Boerwinkle - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
Julie E Buring, Susan E Hankinson, Frank B Hu, Peter Kraft, David J Hunter & Paul M Ridker - Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
Stephen J Chanock & David J Hunter - Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
Marilyn C Cornelis, Frank B Hu, Peter Kraft, Rob M van Dam & David J Hunter - Department of Biostatistics, Collaborative Studies Coordinating Center, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
David Couper - Department of Medicine, Sections of General Internal Medicine, Preventive Medicine and Endocrinology, Boston University School of Medicine, Boston, Massachusetts, USA
Andrea D Coviello & Joanne M Murabito - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Ulf de Faire - Department of Social Medicine, MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK
George Davey Smith - Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Douglas F Easton, Paul Pharoah & Jonathon Tyrer - Department of Oncology, Strangeways Research Laboratories, University of Cambridge, Cambridge, UK
Douglas F Easton, Paul Pharoah & Jonathon Tyrer - Molecular Programming and Research Informatics (MPRI), Merck and Co., Inc., Rahway, New Jersey, USA
Valur Emilsson - National Institute for Health and Welfare, Helsinki, Finland
Johan Eriksson, Leena Peltonen, Anneli Pouta, Veikko Salomaa & Emmi Tikkanen - Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
Johan Eriksson - Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland
Johan Eriksson - Folkhalsan Research Centre, Helsinki, Finland
Johan Eriksson - Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA
Luigi Ferrucci - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
Aaron R Folsom & Ellen W Demerath - Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA
Melissa Garcia, Lenore J Launer & Tamara B Harris - Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
Susan E Hankinson, Frank B Hu, Peter Kraft & David J Hunter - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
Andrew C Heath - Laboratory of Neurogenetics, National Institute of Aging, Bethesda, Maryland, USA
Dena G Hernandez - Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Albert Hofman, Fernando Rivadeneira & André G Uitterlinden - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
Marjo-Riitta Järvelin & Ulla Sovio - National Heart, Lung, and Blood Institute (NHLBI) Center for Population Studies, Bethesda, Maryland, USA
Andrew D Johnson & Daniel Levy - Hebrew Senior Life Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA
David Karasik & Douglas P Kiel - Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
Kay-Tee Khaw - Medical School, University of Zagreb, Zagreb, Croatia
Ivana Kolcic & Ozren Polasek - Department of Obstetrics and Gynaecology, Erasmus, MC, Rotterdam, The Netherlands.,
Joop S E Laven - Human Genetics, Genome Institute of Singapore, Singapore
Jianjun Liu - Division of Cardiology, Boston University School of Medicine, Boston, Massachusetts, USA
Daniel Levy - Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Nicholas G Martin - Department of Social Medicine, Avon Longitudinal Study of Parents and Children (ALSPAC), University of Bristol, Bristol, UK
Wendy L McArdle, Kate Northstone & Susan M Ring - Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, USA
Vincent Mooser & Dawn M Waterworth - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Jeffrey C Murray - Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA
Michael A Nalls - Department of Oral and Dental Science, University of Bristol, Bristol, UK
Andrew R Ness - Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
Ben A Oostra - Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Munro Peacock & Michael J Econs - Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Aarno Palotie, Leena Peltonen & Ayellet V Segrè - Genetic and Molecular Epidemiology Laboratory, McMaster University, Hamilton, Ontario, Canada
Guillaume Paré - Amgen, Cambridge, Massachusetts, USA
Alex N Parker, Kim Tsui & Lauren Young - School of Women's and Infants' Health, The University of Western Australia, Crawley, Australia
Craig E Pennell - Gen-Info Ltd., Zagreb, Croatia
Ozren Polasek - Cardiovascular Disease, Merck Research Laboratory, Rahway, New Jersey, USA
Andrew S Plump - Croatian Centre for Global Health, University of Split Medical School, Split, Croatia
Igor Rudan - Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA
David Schlessinger - Unità Operativa Geriatria-Istituto Nazionale Ricovero e Cura per Anziani (INRCA), IRCCS, Rome, Italy
Angelo Scuteri - Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
Ayellet V Segrè - Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, USA
Alan R Shuldiner - Division of Community Health Sciences, St. George's, University of London, London, UK
David P Strachan - Icelandic Cancer Registry, Reykjavik, Iceland
Laufey Tryggvadottir - Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Rob M van Dam - Department of Medicine, National University of Singapore, Singapore
Rob M van Dam - Department of Internal Medicine, BH-10 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Peter Vollenweider & Gerard Waeber - Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
H Erich Wichmann - Klinikum Grosshadern, Munich, Germany
H Erich Wichmann - Molecular Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Grant W Montgomery - Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
Paul M Ridker - Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Kari Stefansson & Unnur Thorsteinsdottir - Department of Paediatrics, University of Cambridge, Cambridge, UK
Ken K Ong
Authors
- Cathy E Elks
- John R B Perry
- Patrick Sulem
- Daniel I Chasman
- Nora Franceschini
- Chunyan He
- Kathryn L Lunetta
- Jenny A Visser
- Enda M Byrne
- Diana L Cousminer
- Daniel F Gudbjartsson
- Tõnu Esko
- Bjarke Feenstra
- Jouke-Jan Hottenga
- Daniel L Koller
- Zoltán Kutalik
- Peng Lin
- Massimo Mangino
- Mara Marongiu
- Patrick F McArdle
- Albert V Smith
- Lisette Stolk
- Sophie H van Wingerden
- Jing Hua Zhao
- Eva Albrecht
- Tanguy Corre
- Erik Ingelsson
- Caroline Hayward
- Patrik K E Magnusson
- Erin N Smith
- Shelia Ulivi
- Nicole M Warrington
- Lina Zgaga
- Helen Alavere
- Najaf Amin
- Thor Aspelund
- Stefania Bandinelli
- Inês Barroso
- Gerald S Berenson
- Sven Bergmann
- Hannah Blackburn
- Eric Boerwinkle
- Julie E Buring
- Fabio Busonero
- Harry Campbell
- Stephen J Chanock
- Wei Chen
- Marilyn C Cornelis
- David Couper
- Andrea D Coviello
- Pio d'Adamo
- Ulf de Faire
- Eco J C de Geus
- Panos Deloukas
- Angela Döring
- George Davey Smith
- Douglas F Easton
- Gudny Eiriksdottir
- Valur Emilsson
- Johan Eriksson
- Luigi Ferrucci
- Aaron R Folsom
- Tatiana Foroud
- Melissa Garcia
- Paolo Gasparini
- Frank Geller
- Christian Gieger
- Vilmundur Gudnason
- Per Hall
- Susan E Hankinson
- Liana Ferreli
- Andrew C Heath
- Dena G Hernandez
- Albert Hofman
- Frank B Hu
- Thomas Illig
- Marjo-Riitta Järvelin
- Andrew D Johnson
- David Karasik
- Kay-Tee Khaw
- Douglas P Kiel
- Tuomas O Kilpeläinen
- Ivana Kolcic
- Peter Kraft
- Lenore J Launer
- Joop S E Laven
- Shengxu Li
- Jianjun Liu
- Daniel Levy
- Nicholas G Martin
- Wendy L McArdle
- Mads Melbye
- Vincent Mooser
- Jeffrey C Murray
- Sarah S Murray
- Michael A Nalls
- Pau Navarro
- Mari Nelis
- Andrew R Ness
- Kate Northstone
- Ben A Oostra
- Munro Peacock
- Lyle J Palmer
- Aarno Palotie
- Guillaume Paré
- Alex N Parker
- Nancy L Pedersen
- Leena Peltonen
- Craig E Pennell
- Paul Pharoah
- Ozren Polasek
- Andrew S Plump
- Anneli Pouta
- Eleonora Porcu
- Thorunn Rafnar
- John P Rice
- Susan M Ring
- Fernando Rivadeneira
- Igor Rudan
- Cinzia Sala
- Veikko Salomaa
- Serena Sanna
- David Schlessinger
- Nicholas J Schork
- Angelo Scuteri
- Ayellet V Segrè
- Alan R Shuldiner
- Nicole Soranzo
- Ulla Sovio
- Sathanur R Srinivasan
- David P Strachan
- Mar-Liis Tammesoo
- Emmi Tikkanen
- Daniela Toniolo
- Kim Tsui
- Laufey Tryggvadottir
- Jonathon Tyrer
- Manuela Uda
- Rob M van Dam
- Joyce B J van Meurs
- Peter Vollenweider
- Gerard Waeber
- Nicholas J Wareham
- Dawn M Waterworth
- Michael N Weedon
- H Erich Wichmann
- Gonneke Willemsen
- James F Wilson
- Alan F Wright
- Lauren Young
- Guangju Zhai
- Wei Vivian Zhuang
- Laura J Bierut
- Dorret I Boomsma
- Heather A Boyd
- Laura Crisponi
- Ellen W Demerath
- Cornelia M van Duijn
- Michael J Econs
- Tamara B Harris
- David J Hunter
- Ruth J F Loos
- Andres Metspalu
- Grant W Montgomery
- Paul M Ridker
- Tim D Spector
- Elizabeth A Streeten
- Kari Stefansson
- Unnur Thorsteinsdottir
- André G Uitterlinden
- Elisabeth Widen
- Joanne M Murabito
- Ken K Ong
- Anna Murray
Consortia
The GIANT Consortium
Contributions
Writing group: D.I.B., H.A.B., D.I.C., D.L.C., L.C., E.W.D., M.J.E., C.E.E., T.E., B.F., N.F., F.G., D.F.G., C. He, T.B.H., D.J.H., D.L.K., K.K.L., M. Mangino, M. Marongiu, J.M.M., A. Metspalu, A. Murray, K.K.O., J.R.B.P., L.S., E.A.S., P.S., U.T., A.G.U., C.M.v.D., S.H.v.W., J.A.V., E.W., G.Z.
Corresponding authors
Correspondence toJoanne M Murabito, Ken K Ong or Anna Murray.
Ethics declarations
Competing interests
P.S., D.F.G., K.S. and U.T. are employed by deCODE Genetics. V.E. and A. Plump are employed by Merck & Co. V.M. and D.M.W. are employed by GlaxoSmithKline. A. Parker, L.Y. and K.T. are employed by Amgen. I.B. and spouse own stock in Incyte Ltd and GlaxoSmithKline.
Additional information
A full list of members is provided in the Supplementary Note.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–8, Supplementary Tables 1–11 and 13–17 and Supplementary Note. (PDF 3142 kb)
Supplementary Table 12
Age at menarche associations for 8,770 SNPs in 16 candidate genes and their surrounding regions (+/-300kb). (XLS 1749 kb)
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Elks, C., Perry, J., Sulem, P. et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.Nat Genet 42, 1077–1085 (2010). https://doi.org/10.1038/ng.714
- Received: 10 May 2010
- Accepted: 19 October 2010
- Published: 21 November 2010
- Issue date: December 2010
- DOI: https://doi.org/10.1038/ng.714