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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

  • 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. Kilpelänen, 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*
*Corresponding author for this work
  • Cambridge University Hospitals NHS Foundation Trust
  • University of Exeter
  • deCODE Genetics
  • Division of Preventive Medicine
  • Brigham and Women’s Hospital
  • Harvard University
  • Department of Epidemiology
  • University of North Carolina at Chapel Hill
  • Department of Public Health
  • Indiana University Bloomington
  • National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
  • Department of Biostatistics
  • Boston University
  • Department of Internal Medicine
  • Erasmus University Rotterdam
  • Queensland Institute of Medical Research
  • University of Queensland
  • FIMM Institute for Molecular Medicine Finland
  • University of Helsinki
  • University of Tartu
  • Department of Biotechnology
  • Department of Epidemiology Research
  • Statens Serum Institut
  • Vrije Universiteit Amsterdam
  • Medical and Molecular Genetics
  • Department of Medical Genetics
  • University of Lausanne
  • Swiss Institute of Bioinformatics
  • Department of Psychiatry
  • Washington University St. Louis
  • Department of Twin Research and Genetic Epidemiology
  • King's College London
  • Istituto di Neurogeneticae Neurofarmacologia
  • National Research Council of Italy
  • Division of Endocrinology
  • University of Maryland, Baltimore
  • Icelandic Heart Association
  • University of Iceland
  • Netherlands Consortium for Healthy Aging
  • Department of Epidemiology
  • Institute of Epidemiology
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Division of Genetics and Cell Biology
  • San Raffaele Scientific Institute
  • Department of Medical Epidemiology and Biostatistics
  • Karolinska Institutet
  • NHS Lothian
  • Scripps Genomic Medicine
  • Scripps Research Translational Institute
  • Scripps Research Institute
  • Department of Reproductive Sciences and Development
  • University of Trieste
  • Centre for Genetic Epidemiology and Biostatistics
  • University of Western Australia
  • Centre for Population Health Sciences
  • University of Edinburgh
  • Geriatric Unit
  • Wellcome Trust Sanger Institute
  • Tulane University
  • University of Texas Health Science Center at Houston
  • Department of Epidemiology
  • Division of Cancer Epidemiology and Genetics
  • National Institutes of Health
  • Department of Nutrition
  • Department of Medicine
  • Division of Cardiovascular Epidemiology
  • Department of Biological Psychology
  • Children of the Nineties
  • University of Bristol
  • Department of Public Health and Primary Care
  • University of Cambridge
  • Department of Oncology
  • Merck Research Laboratories
  • National Institute for Health and Welfare
  • Department of General Practice and Primary Health Care
  • Unit of General Practice
  • Helsinki University Hospital
  • Folkhalsan
  • Longitudinal Studies Section
  • Division of Epidemiology and Community Health
  • University of Minnesota Twin Cities
  • Laboratory of Epidemiology
  • Channing Division of Network Medicine
  • Laboratory of Neurogenetics
  • National Institute of Aging
  • Department of Epidemiology and Biostatistics
  • Imperial College London
  • Center for Population Studies
  • Hebrew SeniorLife Institute for Aging Research
  • Department of Public Health and Primary Care
  • Medical School
  • University of Zagreb
  • Agency for Science, Technology and Research, Singapore
  • Division of Cardiology
  • Department of Genetic Epidemiology
  • Genetics Division
  • GlaxoSmithKline
  • University of Iowa
  • Laboratory of Neurogenetics
  • School of Oral and Dental Sciences
  • Department of Clinical Genetics
  • Department of Medicine
  • Massachusetts Institute of Technology
  • Genetic and Molecular Epidemiology Laboratory
  • McMaster University
  • Amgen Incorporated
  • Department of Paediatrics
  • Gen-Info Ltd
  • Cardiovascular Diseases
  • University of Split
  • Istituto Nazionale di Riposo e Cura per Anziani - Ancona
  • Department of Molecular Biology
  • Massachusetts General Hospital
  • Geriatric Research and Education Clinical Center
  • Department of Veterans Affairs
  • Division of Community Health Sciences
  • St. George’s Hospital
  • Icelandic Cancer Society
  • Department of Epidemiology and Public Health
  • National University of Singapore
  • Department of Medicine
  • Department of Internal Medicine
  • Institute of Medical Informatics
  • Ludwig Maximilian University of Munich
  • Molecular Epidemiology
  • Division of Cardiology
  • University of Tartu

Research output: Contribution to journalArticlepeer-review

Abstract

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

Original languageEnglish
Pages (from-to)1077-1085
Number of pages9
JournalNature Genetics
Volume42
Issue number12
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

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