Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-10

AUTHORS

John RB Perry, Felix Day, Cathy E Elks, Patrick Sulem, Deborah J Thompson, Teresa Ferreira, Chunyan He, Daniel I Chasman, Tõnu Esko, Gudmar Thorleifsson, Eva Albrecht, Wei Q Ang, Tanguy Corre, Diana L Cousminer, Bjarke Feenstra, Nora Franceschini, Andrea Ganna, Andrew D Johnson, Sanela Kjellqvist, Kathryn L Lunetta, George McMahon, Ilja M Nolte, Lavinia Paternoster, Eleonora Porcu, Albert V Smith, Lisette Stolk, Alexander Teumer, Natalia Tšernikova, Emmi Tikkanen, Sheila Ulivi, Erin K Wagner, Najaf Amin, Laura J Bierut, Enda M Byrne, Jouke-Jan Hottenga, Daniel L Koller, Massimo Mangino, Tune H Pers, Laura M Yerges-Armstrong, Jing Hua Zhao, Irene L Andrulis, Hoda Anton-Culver, Femke Atsma, Stefania Bandinelli, Matthias W Beckmann, Javier Benitez, Carl Blomqvist, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Julie E Buring, Jenny Chang-Claude, Stephen Chanock, Jinhui Chen, Georgia Chenevix-Trench, J. Margriet Collée, Fergus J Couch, David Couper, Andrea D Coveillo, Angela Cox, Kamila Czene, Adamo Pio D’adamo, George Davey Smith, Immaculata De Vivo, Ellen W Demerath, Joe Dennis, Peter Devilee, Aida K Dieffenbach, Alison M Dunning, Gudny Eiriksdottir, Johan G Eriksson, Peter A Fasching, Luigi Ferrucci, Dieter Flesch-Janys, Henrik Flyger, Tatiana Foroud, Lude Franke, Melissa E Garcia, Montserrat García-Closas, Frank Geller, Eco EJ de Geus, Graham G Giles, Daniel F Gudbjartsson, Vilmundur Gudnason, Pascal Guénel, Suiqun Guo, Per Hall, Ute Hamann, Robin Haring, Catharina A Hartman, Andrew C Heath, Albert Hofman, Maartje J Hooning, John L Hopper, Frank B Hu, David J Hunter, David Karasik, Douglas P Kiel, Julia A Knight, Veli-Matti Kosma, Zoltan Kutalik, Sandra Lai, Diether Lambrechts, Annika Lindblom, Reedik Mägi, Patrik K Magnusson, Arto Mannermaa, Nicholas G Martin, Gisli Masson, Patrick F McArdle, Wendy L McArdle, Mads Melbye, Kyriaki Michailidou, Evelin Mihailov, Lili Milani, Roger L Milne, Heli Nevanlinna, Patrick Neven, Ellen A Nohr, Albertine J Oldehinkel, Ben A Oostra, Aarno Palotie, Munro Peacock, Nancy L Pedersen, Paolo Peterlongo, Julian Peto, Paul DP Pharoah, Dirkje S Postma, Anneli Pouta, Katri Pylkäs, Paolo Radice, Susan Ring, Fernando Rivadeneira, Antonietta Robino, Lynda M Rose, Anja Rudolph, Veikko Salomaa, Serena Sanna, David Schlessinger, Marjanka K Schmidt, Mellissa C Southey, Ulla Sovio, Meir J Stampfer, Doris Stöckl, Anna M Storniolo, Nicholas J Timpson, Jonathan Tyrer, Jenny A Visser, Peter Vollenweider, Henry Völzke, Gerard Waeber, Melanie Waldenberger, Henri Wallaschofski, Qin Wang, Gonneke Willemsen, Robert Winqvist, Bruce HR Wolffenbuttel, Margaret J Wright, , , , , , , Dorret I Boomsma, Michael J Econs, Kay-Tee Khaw, Ruth JF Loos, Mark I McCarthy, Grant W Montgomery, John P Rice, Elizabeth A Streeten, Unnur Thorsteinsdottir, Cornelia M van Duijn, Behrooz Z Alizadeh, Sven Bergmann, Eric Boerwinkle, Heather A Boyd, Laura Crisponi, Paolo Gasparini, Christian Gieger, Tamara B Harris, Erik Ingelsson, Marjo-Riitta Järvelin, Peter Kraft, Debbie Lawlor, Andres Metspalu, Craig E Pennell, Paul M Ridker, Harold Snieder, Thorkild IA Sørensen, Tim D Spector, David P Strachan, André G Uitterlinden, Nicholas J Wareham, Elisabeth Widen, Marek Zygmunt, Anna Murray, Douglas F Easton, Kari Stefansson, Joanne M Murabito, Ken K Ong

ABSTRACT

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 × 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 γ-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. More... »

PAGES

92

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  • Journal

    TITLE

    Nature

    ISSUE

    7520

    VOLUME

    514

    Author Affiliations

  • King's College London
  • University of Cambridge
  • deCODE Genetics (Iceland)
  • Wellcome Centre for Human Genetics
  • Indiana University – Purdue University Indianapolis
  • Harvard University
  • Helmholtz Zentrum München
  • University of Western Australia
  • Swiss Institute of Bioinformatics
  • University of Helsinki
  • Statens Serum Institut
  • University of North Carolina System
  • Karolinska Institute
  • Boston University
  • University of Bristol
  • University Medical Center Groningen
  • University of Sassari
  • University of Iceland
  • Erasmus University Medical Center
  • University of Greifswald
  • University of Tartu
  • Washington University in St. Louis
  • QIMR Berghofer Medical Research Institute
  • VU University Amsterdam
  • Broad Institute
  • University of Maryland, Baltimore
  • University of Toronto
  • University of California, Irvine
  • Sanquin
  • Azienda Sanitaria di Firenze
  • Spanish National Cancer Research Centre
  • Helsinki University Central Hospital
  • European Institute of Oncology
  • University of Tübingen
  • German Cancer Research Center
  • National Cancer Institute
  • Mayo Clinic
  • Boston University School of Medicine
  • University of Sheffield
  • University of Trieste
  • Brigham and Women's Hospital
  • University of Minnesota
  • Leiden University Medical Center
  • Icelandic Heart Association
  • Folkhälsans Forskningscentrum
  • National Institute on Aging
  • University Medical Center Hamburg-Eppendorf
  • National Institutes of Health
  • Institute of Cancer Research
  • EMGO Institute for Health and Care Research
  • University of Melbourne
  • University of Paris-Sud
  • Southern Medical University
  • Kuopio University Hospital
  • National Research Council
  • KU Leuven
  • Stanford University
  • University of Southern Denmark
  • Massachusetts General Hospital
  • FIRC Institute of Molecular Oncology
  • London School of Hygiene & Tropical Medicine
  • Oulu University Hospital
  • University of Oulu
  • Istituto Nazionale dei Tumori
  • National Institute for Health and Welfare
  • Antoni van Leeuwenhoek Hospital
  • Ludwig Maximilian University of Munich
  • University Hospital of Lausanne
  • German Centre for Cardiovascular Research
  • Peter MacCallum Cancer Centre
  • Icahn School of Medicine at Mount Sinai
  • University of Oxford
  • Centre for Medical Systems Biology
  • University of Houston
  • Uppsala University
  • Copenhagen University Hospital
  • University College London
  • University of Exeter
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature13545

    DOI

    http://dx.doi.org/10.1038/nature13545

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1007797493

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25231870


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    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature13545'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature13545'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature13545'

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