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

Journal article


Publication Details

Author(s): Perry JRB, Day F, Elks CE, Sulem P, Thompson DJ, Ferreira T, He C, Chasman DI, Esko T, Thorleifsson G, Albrecht E, Ang WQ, Corre T, Cousminer DL, Feenstra B, Franceschini N, Ganna A, Johnson AD, Kjellqvist S, Lunetta KL, Mcmahon G, Nolte IM, Paternoster L, Porcu E, Smith AV, Stolk L, Teumer A, Tsernikova N, Tikkanen E, Ulivi S, Wagner EK, Amin N, Bierut LJ, Byrne EM, Hottenga JJ, Koller DL, Mangino M, Pers TH, Yerges-Armstrong LM, Zhao JH, Andrulis IL, Anton-Culver H, Atsma F, Bandinelli S, Beckmann M, Benitez J, Blomqvist C, Bojesen SE, Bolla MK, Bonanni B, Brauch H, Brenner H, Buring JE, Chang-Claude J, Chanock S, Chen J, Chenevix-Trench G, Collee JM, Couch FJ, Couper D, Coviello AD, Cox A, Czene K, D'Adamo AP, Smith GD, De Vivo I, Demerath EW, Dennis J, Devilee P, Dieffenbach AK, Dunning AM, Eiriksdottir G, Eriksson JG, Fasching P, Ferrucci L, Flesch-Janys D, Flyger H, Foroud T, Franke L, Garcia ME, Garcia-Closas M, Geller F, De Geus EEJ, Giles GG, Gudbjartsson DF, Gudnason V, Guenel P, Guo S, Hall P, Hamann U, Haring R, Hartman CA, Heath A, Hofman A, Hooning MJ, Hopper JL, Hu FB, Hunter DJ, Karasik D, Kiel DP, Knight JA, Kosma VM, Kutalik Z, Lai S, Lambrechts D, Lindblom A, Maegi R, Magnusson PK, Mannermaa A, Martin NG, Masson G, Mcardle PF, Mcardle WL, Melbye M, Michailidou K, Mihailov E, Milani L, Milne RL, Nevanlinna H, Neven P, Nohr EA, Oldehinkel AJ, Oostra BA, Palotie A, Peacock M, Pedersen NL, Peterlongo P, Peto J, Pharoah PDP, Postma DS, Pouta A, Pylkaes K, Radice P, Ring S, Rivadeneira F, Robino A, Rose LM, Rudolph A, Salomaa V, Sanna S, Schlessinger D, Schmidt MK, Southey MC, Sovio U, Stampfer MJ, Stoeckl D, Storniolo AM, Timpson NJ, Tyrer J, Visser JA, Vollenweider P, Voelzke H, Waeber G, Waldenberger M, Wallaschofski H, Wang Q, Willemsen G, Winqvist R, Wolffenbuttel BHR, Wright MJ, Boomsma DI, Econs MJ, Khaw KT, Loos RJF, Mccarthy MI, Montgomery GW, Rice JP, Streeten EA, Thorsteinsdottir U, Van Duijn CM, Alizadeh BZ, Bergmann S, Boerwinkle E, Boyd HA, Crisponi L, Gasparini P, Gieger C, Harris TB, Ingelsson E, Jaervelin MR, Kraft P, Lawlor D, Metspalu A, Pennell CE, Ridker PM, Snieder H, Sorensen TIA, Spector TD, Strachan DP, Uitterlinden AG, Wareham NJ, Widen E, Zygmunt M, Murray A, Easton DF, Stefansson K, Murabito JM, Ong KK
Journal: Nature
Publication year: 2014
Volume: 514
Journal issue: 7520
Pages range: 92-7
ISSN: 0028-0836


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 ?-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.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


External institutions with authors

Antoni van Leeuwenhoek
Boston Children's Hospital
Boston University
Brigham and Women's Hospital (BWH)
Cancer Council Victoria
Consiglio Nazionale delle Ricerche (CNR)
Copenhagen University Hospital
deCODE genetics
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Erasmus University Medical Center (MC)
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Harvard University
Hebrew SeniorLife
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Helsingin yliopisto / University of Helsinki
Icelandic Heart Association (IHA)
IFOM - FIRC Institute of Molecular Oncology
Imperial College London / The Imperial College of Science, Technology and Medicine
Indiana University
IRCCS Ospedale Infantile Burlo Garofolo
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
King’s College London
Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV)
Leiden University
Massachusetts Institute of Technology (MIT)
Mayo Clinic
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
National Institute for Health and Welfare (THL)
Netherlands Consortium for Healthy Ageing (NCHA)
Oulun Yliopisto / University of Oulo
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Robert-Bosch-Krankenhaus
Sanquin Bloedbank Nijmegen
Southern Medical University / 南方医科大学
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Statens Serum Institut
The University of Melbourne
Tuscany Regional Health Agency
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
Université de Lausanne (UNIL)
University College London (UCL)
University of Bristol
University of California Irvine
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Exeter
University of Groningen / Rijksuniversiteit Groningen
University of Houston
University of Maryland
University of Minnesota (UMN)
University of North Carolina at Chapel Hill
University of Oxford
University of Queensland
University of Sheffield
University of Southern Denmark / Syddansk Universitet
University of Tartu
University of Western Australia (UWA)
Uppsala University
US National Institutes of Health (NIH)
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Washington University


How to cite

APA:
Perry, J.R.B., Day, F., Elks, C.E., Sulem, P., Thompson, D.J., Ferreira, T.,... Ong, K.K. (2014). Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature, 514(7520), 92-7. https://dx.doi.org/10.1038/nature13545

MLA:
Perry, John R. B., et al. "Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche." Nature 514.7520 (2014): 92-7.

BibTeX: 

Last updated on 2019-21-07 at 08:05