IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-017-02662-2.html
   My bibliography  Save this article

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author

Listed:
  • Xia Jiang

    (Harvard T.H.Chan School of Public Health
    Karolinska Institutet)

  • Paul F. O’Reilly

    (Institute of Psychiatry)

  • Hugues Aschard

    (Harvard T.H.Chan School of Public Health
    Institut Pasteur)

  • Yi-Hsiang Hsu

    (Institute for Aging Research
    Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of Harvard and Massachusetts Institute of Technology)

  • J. Brent Richards

    (Human Genetics, Epidemiology and Biostatistics)

  • Josée Dupuis

    (Boston University School of Public Health
    Framingham Heart Study)

  • Erik Ingelsson

    (Stanford University School of Medicine Stanford
    Uppsala University)

  • David Karasik

    (Institute for Aging Research)

  • Stefan Pilz

    (Medical University of Graz)

  • Diane Berry

    (University College London, Great Ormond Street, Institute of Child Health)

  • Bryan Kestenbaum

    (Kidney Research Institute, Division of Nephrology)

  • Jusheng Zheng

    (University of Cambridge School of Clinical Medicine)

  • Jianan Luan

    (University of Cambridge School of Clinical Medicine)

  • Eleni Sofianopoulou

    (University of Cambridge, Strangeways Research Laboratory)

  • Elizabeth A. Streeten

    (University of Maryland School of Medicine)

  • Demetrius Albanes

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH)

  • Pamela L. Lutsey

    (University of Minnesota)

  • Lu Yao

    (University of Minnesota)

  • Weihong Tang

    (University of Minnesota)

  • Michael J. Econs

    (Indiana University, Endocrinology)

  • Henri Wallaschofski

    (University Medicine Greifswald
    DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald)

  • Henry Völzke

    (DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald
    Universitätsmedizin Greifswald)

  • Ang Zhou

    (University of South Australia)

  • Chris Power

    (University College London, Great Ormond Street, Institute of Child Health)

  • Mark I. McCarthy

    (University of Oxford
    University of Oxford
    Oxford NIHR Biomedical Research Centre, Churchill Hospital)

  • Erin D. Michos

    (Johns Hopkins School of Medicine
    Johns Hopkins Bloomberg School of Public Health)

  • Eric Boerwinkle

    (University of Texas Health Science Center at Houston)

  • Stephanie J. Weinstein

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH)

  • Neal D. Freedman

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH)

  • Wen-Yi Huang

    (National Cancer Institute, NIH)

  • Natasja M. Schoor

    (Amsterdam Public Health Research Institute, VU University Medical Center)

  • Nathalie Velde

    (Erasmus MC Department of Epidemiology
    AMC, Internal Medicine, Geriatrics Department)

  • Lisette C. P. G. M. de Groot

    (Wageningen University)

  • Anke Enneman

    (Erasmus MC Department of Epidemiology)

  • L. Adrienne Cupples

    (Boston University School of Public Health
    Framingham Heart Study)

  • Sarah L. Booth

    (Tufts University)

  • Ramachandran S. Vasan

    (Framingham Heart Study)

  • Ching-Ti Liu

    (Boston University School of Public Health)

  • Yanhua Zhou

    (Boston University School of Public Health)

  • Samuli Ripatti

    (University of Helsinki)

  • Claes Ohlsson

    (University of Gothenburg)

  • Liesbeth Vandenput

    (University of Gothenburg)

  • Mattias Lorentzon

    (University of Gothenburg and Sahlgrenska University Hospital)

  • Johan G. Eriksson

    (University of Helsinki and Helsinki University Hospital, University of Helsinki
    University of Helsinki)

  • M. Kyla Shea

    (Tufts University)

  • Denise K. Houston

    (Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Medical Center Boulevard)

  • Stephen B. Kritchevsky

    (Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Medical Center Boulevard)

  • Yongmei Liu

    (Wake Forest School of Medicine)

  • Kurt K. Lohman

    (Wake Forest School of Medicine)

  • Luigi Ferrucci

    (Longitudinal Studies Section, Intramural Research Program of the National Institute on Aging, NIH)

  • Munro Peacock

    (Indiana University, Endocrinology)

  • Christian Gieger

    (German Research Center for Environmental Health, Molecular Epidemiology, AME, Ingolstädter Landstr 1)

  • Marian Beekman

    (Molecular Epidemiology, Leiden University Medical Center, Einthovenweg 20)

  • Eline Slagboom

    (Molecular Epidemiology, Leiden University Medical Center, Einthovenweg 20)

  • Joris Deelen

    (Molecular Epidemiology, Leiden University Medical Center, Einthovenweg 20
    Max Planck Institute for Biology of Ageing)

  • Diana van Heemst

    (Leiden University Medical Center)

  • Marcus E. Kleber

    (University of Heidelberg)

  • Winfried März

    (University of Heidelberg
    Medical University of Graz
    SYNLAB Holding Deutschland GmbH)

  • Ian H. Boer

    (University of Washington)

  • Alexis C. Wood

    (USDA/ARS Children’s Nutrition Research Center)

  • Jerome I. Rotter

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center)

  • Stephen S. Rich

    (University of Virginia
    University of Virginia)

  • Cassianne Robinson-Cohen

    (Vanderbilt University Medical Center)

  • Martin Heijer

    (Erasmus MC Department of Internal Medicine)

  • Marjo-Riitta Jarvelin

    (Imperial College London
    University of Oulu
    Biocenter Oulu, University of Oulu
    Oulu University Hospital)

  • Alana Cavadino

    (University College London, Great Ormond Street, Institute of Child Health
    Queen Mary University of London)

  • Peter K. Joshi

    (University of Edinburgh)

  • James F. Wilson

    (University of Edinburgh
    the University of Edinburgh, Western General Hospital)

  • Caroline Hayward

    (the University of Edinburgh, Western General Hospital)

  • Lars Lind

    (Uppsala University)

  • Karl Michaëlsson

    (Uppsala University)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • M. Carola Zillikens

    (Erasmus MC Department of Internal Medicine)

  • Andre G. Uitterlinden

    (Erasmus MC Department of Epidemiology
    Erasmus MC Department of Internal Medicine)

  • Fernando Rivadeneira

    (Erasmus MC Department of Epidemiology
    Erasmus MC Department of Internal Medicine)

  • Linda Broer

    (Erasmus MC Department of Internal Medicine)

  • Lina Zgaga

    (University of Dublin)

  • Harry Campbell

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Evropi Theodoratou

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Susan M. Farrington

    (University of Edinburgh, Western General Hospital)

  • Maria Timofeeva

    (University of Edinburgh, Western General Hospital)

  • Malcolm G. Dunlop

    (University of Edinburgh, Western General Hospital)

  • Ana M. Valdes

    (King’s College London, St Thomas’ Campus
    University of Nottingham)

  • Emmi Tikkanen

    (University of Helsinki)

  • Terho Lehtimäki

    (Department of Clinical Chemistry, Fimlab Laboratories
    University of Tampere)

  • Leo-Pekka Lyytikäinen

    (Department of Clinical Chemistry, Fimlab Laboratories
    University of Tampere)

  • Mika Kähönen

    (Tampere University Hospital
    University of Tampere)

  • Olli T. Raitakari

    (Turku University Hospital
    University of Turku)

  • Vera Mikkilä

    (Science Adviser at Academy of Finland)

  • M. Arfan Ikram

    (Erasmus MC Department of Epidemiology)

  • Naveed Sattar

    (BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University Avenue)

  • J. Wouter Jukema

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Nicholas J. Wareham

    (University of Cambridge School of Clinical Medicine)

  • Claudia Langenberg

    (University of Cambridge School of Clinical Medicine)

  • Nita G. Forouhi

    (University of Cambridge School of Clinical Medicine)

  • Thomas E. Gundersen

    (Vitas AS)

  • Kay-Tee Khaw

    (University of Cambridge, Strangeways Research Laboratory)

  • Adam S. Butterworth

    (University of Cambridge, Strangeways Research Laboratory)

  • John Danesh

    (University of Cambridge, Strangeways Research Laboratory
    Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Timothy Spector

    (King’s College London, St Thomas’ Campus)

  • Thomas J. Wang

    (Vanderbilt Heart and Vascular Institute)

  • Elina Hyppönen

    (University College London, Great Ormond Street, Institute of Child Health
    University of South Australia)

  • Peter Kraft

    (Harvard T.H.Chan School of Public Health)

  • Douglas P. Kiel

    (Institute for Aging Research
    Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of Harvard and Massachusetts Institute of Technology)

Abstract

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Suggested Citation

  • Xia Jiang & Paul F. O’Reilly & Hugues Aschard & Yi-Hsiang Hsu & J. Brent Richards & Josée Dupuis & Erik Ingelsson & David Karasik & Stefan Pilz & Diane Berry & Bryan Kestenbaum & Jusheng Zheng & Jiana, 2018. "Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02662-2
    DOI: 10.1038/s41467-017-02662-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-02662-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-02662-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Robyn M. Lucas & Rachael M. Rodney Harris, 2018. "On the Nature of Evidence and ‘Proving’ Causality: Smoking and Lung Cancer vs. Sun Exposure, Vitamin D and Multiple Sclerosis," IJERPH, MDPI, vol. 15(8), pages 1-13, August.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02662-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.