Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-03

AUTHORS

Lisette Stolk, John R B Perry, Daniel I Chasman, Chunyan He, Massimo Mangino, Patrick Sulem, Maja Barbalic, Linda Broer, Enda M Byrne, Florian Ernst, Tõnu Esko, Nora Franceschini, Daniel F Gudbjartsson, Jouke-Jan Hottenga, Peter Kraft, Patrick F McArdle, Eleonora Porcu, So-Youn Shin, Albert V Smith, Sophie van Wingerden, Guangju Zhai, Wei V Zhuang, Eva Albrecht, Behrooz Z Alizadeh, Thor Aspelund, Stefania Bandinelli, Lovorka Barac Lauc, Jacques S Beckmann, Mladen Boban, Eric Boerwinkle, Frank J Broekmans, Andrea Burri, Harry Campbell, Stephen J Chanock, Constance Chen, Marilyn C Cornelis, Tanguy Corre, Andrea D Coviello, Pio d'Adamo, Gail Davies, Ulf de Faire, Eco J C de Geus, Ian J Deary, George V Z Dedoussis, Panagiotis Deloukas, Shah Ebrahim, Gudny Eiriksdottir, Valur Emilsson, Johan G Eriksson, Bart C J M Fauser, Liana Ferreli, Luigi Ferrucci, Krista Fischer, Aaron R Folsom, Melissa E Garcia, Paolo Gasparini, Christian Gieger, Nicole Glazer, Diederick E Grobbee, Per Hall, Toomas Haller, Susan E Hankinson, Merli Hass, Caroline Hayward, Andrew C Heath, Albert Hofman, Erik Ingelsson, A Cecile J W Janssens, Andrew D Johnson, David Karasik, Sharon L R Kardia, Jules Keyzer, Douglas P Kiel, Ivana Kolcic, Zoltán Kutalik, Jari Lahti, Sandra Lai, Triin Laisk, Joop S E Laven, Debbie A Lawlor, Jianjun Liu, Lorna M Lopez, Yvonne V Louwers, Patrik K E Magnusson, Mara Marongiu, Nicholas G Martin, Irena Martinovic Klaric, Corrado Masciullo, Barbara McKnight, Sarah E Medland, David Melzer, Vincent Mooser, Pau Navarro, Anne B Newman, Dale R Nyholt, N Charlotte Onland-Moret, Aarno Palotie, Guillaume Paré, Alex N Parker, Nancy L Pedersen, Petra H M Peeters, Giorgio Pistis, Andrew S Plump, Ozren Polasek, Victor J M Pop, Bruce M Psaty, Katri Räikkönen, Emil Rehnberg, Jerome I Rotter, Igor Rudan, Cinzia Sala, Andres Salumets, Angelo Scuteri, Andrew Singleton, Jennifer A Smith, Harold Snieder, Nicole Soranzo, Simon N Stacey, John M Starr, Maria G Stathopoulou, Kathleen Stirrups, Ronald P Stolk, Unnur Styrkarsdottir, Yan V Sun, Albert Tenesa, Barbara Thorand, Daniela Toniolo, Laufey Tryggvadottir, Kim Tsui, Sheila Ulivi, Rob M van Dam, Yvonne T van der Schouw, Carla H van Gils, Peter van Nierop, Jacqueline M Vink, Peter M Visscher, Marlies Voorhuis, Gérard Waeber, Henri Wallaschofski, H Erich Wichmann, Elisabeth Widen, Colette J M Wijnands-van Gent, Gonneke Willemsen, James F Wilson, Bruce H R Wolffenbuttel, Alan F Wright, Laura M Yerges-Armstrong, Tatijana Zemunik, Lina Zgaga, M Carola Zillikens, Marek Zygmunt, The LifeLines Cohort Study, Alice M Arnold, Dorret I Boomsma, Julie E Buring, Laura Crisponi, Ellen W Demerath, Vilmundur Gudnason, Tamara B Harris, Frank B Hu, David J Hunter, Lenore J Launer, Andres Metspalu, Grant W Montgomery, Ben A Oostra, Paul M Ridker, Serena Sanna, David Schlessinger, Tim D Spector, Kari Stefansson, Elizabeth A Streeten, Unnur Thorsteinsdottir, Manuela Uda, André G Uitterlinden, Cornelia M van Duijn, Henry Völzke, Anna Murray, Joanne M Murabito, Jenny A Visser, Kathryn L Lunetta

ABSTRACT

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. More... »

PAGES

260

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    3

    VOLUME

    44

    Author Affiliations

  • Netherlands Consortium for Healthy Ageing
  • Wellcome Centre for Human Genetics
  • Harvard University
  • Indiana University – Purdue University Indianapolis
  • King's College London
  • deCODE Genetics (Iceland)
  • The University of Texas Health Science Center at Houston
  • Erasmus University Medical Center
  • QIMR Berghofer Medical Research Institute
  • University of Greifswald
  • University of Tartu
  • University of North Carolina at Chapel Hill
  • VU University Amsterdam
  • Broad Institute
  • University of Maryland, Baltimore
  • Institute of Genetic and Biomedical Research
  • Wellcome Sanger Institute
  • University of Iceland
  • Memorial University of Newfoundland
  • Boston University
  • Helmholtz Zentrum München
  • Azienda Sanitaria di Firenze
  • Croatian Science Foundation
  • University Hospital of Lausanne
  • University of Split
  • University Medical Center Utrecht
  • University of Edinburgh
  • National Institutes of Health
  • San Raffaele Hospital
  • National Heart Lung and Blood Institute
  • University of Trieste
  • Karolinska Institute
  • EMGO Institute for Health and Care Research
  • Harokopio University
  • London School of Hygiene & Tropical Medicine
  • Icelandic Heart Association
  • Vaasa Central Hospital
  • National Institute on Aging
  • University of Minnesota
  • Boston University School of Medicine
  • Washington University in St. Louis
  • University of Michigan–Ann Arbor
  • Swiss Institute of Bioinformatics
  • University of Helsinki
  • University of Bristol
  • Genome Institute of Singapore
  • University of Washington
  • University of Exeter
  • GlaxoSmithKline (United States)
  • University of Pittsburgh
  • Helsinki University Central Hospital
  • McMaster University
  • Roche (United States)
  • Imperial College London
  • MSD (United States)
  • Tilburg University
  • Group Health Cooperative
  • Cedars-Sinai Medical Center
  • Competence Centre on Health Technologies (Estonia)
  • University of Lorraine
  • Emory University
  • Roslin Institute
  • Istituto di Genetica Molecolare
  • Amgen (United States)
  • National University of Singapore
  • Hôpital Orthopédique de la Suisse Romande
  • Klinikum der Universität München
  • Praktijkondersteuning Zuidoost-Brabant
  • University of Zagreb
  • Brigham and Women's Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.1051

    DOI

    http://dx.doi.org/10.1038/ng.1051

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053416036

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22267201


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