Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Year: 2018
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: 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. Van Schoor, Nathalie van der 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. de Boer, Alexis C. Wood, Jerome I. Rotter, Stephen S. Rich, Cassianne Robinson-Cohen, Martin den 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, Douglas P. Kiel
Institutions: Harvard University, Karolinska Institutet, King's College London, Institut Pasteur, Broad Institute, Beth Israel Deaconess Medical Center, Hebrew SeniorLife, Massachusetts Institute of Technology, Boston University, Framingham Heart Study, Uppsala University, Stanford Medicine, Stanford Cardiovascular Institute, Stanford University, Medical University of Graz, University College London, University of Cambridge, MRC Epidemiology Unit, University of Maryland, Baltimore, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of Minnesota, Indiana University Indianapolis, Indiana University School of Medicine, Universitätsmedizin Greifswald, German Centre for Cardiovascular Research, University of South Australia, Centre for Human Genetics, Churchill Hospital, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford Centre for Diabetes, Endocrinology and Metabolism, Johns Hopkins University, Johns Hopkins Medicine, The University of Texas Health Science Center at Houston, Amsterdam Public Health, Amsterdam UMC Location Vrije Universiteit Amsterdam, Erasmus MC, Amsterdam UMC Location University of Amsterdam, Wageningen University & Research, Tufts University, Jean Mayer Human Nutrition Research Center on Aging, University of Helsinki, University of Gothenburg, Sahlgrenska University Hospital, Helsinki University Hospital, Wake Forest University Health Sciences, Wake Forest University, Atrium Health Wake Forest Baptist, National Institute on Aging, Helmholtz Munich, Leiden University Medical Center, Max Planck Institute for Biology of Ageing, Heidelberg University, Medizinische Fakultät Mannheim, Synlab (Germany), University of Washington, Agricultural Research Service, Children's Nutrition Research Center at Baylor College of Medicine, The Lundquist Institute, Harbor–UCLA Medical Center, University of Virginia, Vanderbilt University Medical Center, Oulu University Hospital, Imperial College London, University of Oulu, Queen Mary University of London, University of Edinburgh, Western General Hospital, Institute of Genetics and Cancer, MRC Human Genetics Unit, Trinity College Dublin, University of Nottingham, Nottingham City Hospital, Institute for Molecular Medicine Finland, Tampere University, Fimlab (Finland), University of Tampere, Tampere University Hospital, University of Turku, Turku University Hospital, Research Council of Finland, University of Glasgow, Vitas (Norway), Wellcome Sanger Institute, Vanderbilt University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, Economic and Social Research Council, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: G1493513681, NIHR Senior Investigator Award, Parathyroid Hormone: Genetic Architecture and Clinical Consequences, G2826529823, G3445821079, G3600123142, G3682927731, Identifying Osteoporosis Genes by Whole Genome Sequencing and Functional Validation in Zebra Fish, G385201875, G3860752689, G4211044638, G4593371902, Vitamin D and the risk of cardiovascular disease and related traits: a large-scale genetic association study, G55425794, G5730093866, NIHR Senior Investigator Award, G5897142711, G6103829021, NIHR Senior Investigator Award, G6594529311, METADAC Data Access Committee, G6957823285, METADAC, G7964317829, G8330560607, RENEWAL: Systematic approaches to the evaluation of emerging coronary risk markers. Large-scale epidemiological analyses of existing data and stored biological samples, G8451937923, NIHR Senior Investigator Award, NIHR Senior Investigator Award, G8733555866, G8771004808, Novel Molecular Biomarkers of Bone Microarchitecture, Diabetes Research Center (DRC), UCLA Clinical and Translational Science Institute
OpenAlex ID: W2783489228