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

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, Jianan Luan, Eleni Sofianopoulou, Elizabeth A. Streeten, Demetrius Albanes, Pamela L. Lutsey, Lu Yao, Weihong Tang, Michael J. Econs, Henri Wallaschofski, Henry Völzke, Ang Zhou, Chris Power, Mark I. McCarthy, Erin D. Michos, Eric Boerwinkle, Stephanie J. Weinstein, Neal D. Freedman, Wen-Yi Huang, Natasja M. Schoor, Nathalie Velde, Lisette C. P. G. M. de Groot, Anke Enneman, L. Adrienne Cupples, Sarah L. Booth, Ramachandran S. Vasan, Ching-Ti Liu, Yanhua Zhou, Samuli Ripatti, Claes Ohlsson, Liesbeth Vandenput, Mattias Lorentzon, Johan G. Eriksson, M. Kyla Shea, Denise K. Houston, Stephen B. Kritchevsky, Yongmei Liu, Kurt K. Lohman, Luigi Ferrucci, Munro Peacock, Christian Gieger, Marian Beekman, Eline Slagboom, Joris Deelen, Diana van Heemst, Marcus E. Kleber, Winfried März, Ian H. Boer, Alexis C. Wood, Jerome I. Rotter, Stephen S. Rich, Cassianne Robinson-Cohen, Martin Heijer, Marjo-Riitta Jarvelin, Alana Cavadino, Peter K. Joshi, James F. Wilson, Caroline Hayward, Lars Lind, Karl Michaëlsson, Stella Trompet, M. Carola Zillikens, Andre G. Uitterlinden, Fernando Rivadeneira, Linda Broer, Lina Zgaga, Harry Campbell, Evropi Theodoratou, Susan M. Farrington, Maria Timofeeva, Malcolm G. Dunlop, Ana M. Valdes, Emmi Tikkanen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Mika Kähönen, Olli T. Raitakari, Vera Mikkilä, M. Arfan Ikram, Naveed Sattar, J. Wouter Jukema, Nicholas J. Wareham, Claudia Langenberg, Nita G. Forouhi, Thomas E. Gundersen, Kay-Tee Khaw, Adam S. Butterworth, John Danesh, Timothy Spector, Thomas J. Wang, Elina Hyppönen (), Peter Kraft and Douglas P. Kiel ()
Additional contact information
Xia Jiang: Harvard T.H.Chan School of Public Health
Paul F. O’Reilly: Institute of Psychiatry
Hugues Aschard: Harvard T.H.Chan School of Public Health
Yi-Hsiang Hsu: Institute for Aging Research
J. Brent Richards: Human Genetics, Epidemiology and Biostatistics
Josée Dupuis: Boston University School of Public Health
Erik Ingelsson: Stanford University School of Medicine Stanford
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
Henry Völzke: DZHK (German Centre for Cardiovascular Research), Partner Site, 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
Erin D. Michos: Johns Hopkins School of Medicine
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
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
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
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
Diana van Heemst: Leiden University Medical Center
Marcus E. Kleber: University of Heidelberg
Winfried März: University of Heidelberg
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
Cassianne Robinson-Cohen: Vanderbilt University Medical Center
Martin Heijer: Erasmus MC Department of Internal Medicine
Marjo-Riitta Jarvelin: Imperial College London
Alana Cavadino: University College London, Great Ormond Street, Institute of Child Health
Peter K. Joshi: University of Edinburgh
James F. Wilson: University of Edinburgh
Caroline Hayward: the University of Edinburgh, Western General Hospital
Lars Lind: Uppsala University
Karl Michaëlsson: Uppsala University
Stella Trompet: Leiden University Medical Center
M. Carola Zillikens: Erasmus MC Department of Internal Medicine
Andre G. Uitterlinden: Erasmus MC Department of Epidemiology
Fernando Rivadeneira: Erasmus MC Department of Epidemiology
Linda Broer: Erasmus MC Department of Internal Medicine
Lina Zgaga: University of Dublin
Harry Campbell: University of Edinburgh
Evropi Theodoratou: University of Edinburgh
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
Emmi Tikkanen: University of Helsinki
Terho Lehtimäki: Department of Clinical Chemistry, Fimlab Laboratories
Leo-Pekka Lyytikäinen: Department of Clinical Chemistry, Fimlab Laboratories
Mika Kähönen: Tampere University Hospital
Olli T. Raitakari: Turku University Hospital
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
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
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
Peter Kraft: Harvard T.H.Chan School of Public Health
Douglas P. Kiel: Institute for Aging Research

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02662-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02662-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02662-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().