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

Jiang, Xia, O’Reilly, Paul F., Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J. Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A., Albanes, Demetrius, Lutsey, Pamela L., Yao, Lu, Tang, Weihong, Econs, Michael J., Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I., Michos, Erin D., Boerwinkle, Eric, Weinstein, Stephanie J., Freedman, Neal D., Huang, Wen-Yi, Van Schoor, Natasja M., van der Velde, Nathalie, Groot, Lisette C. P. G. M. de, Enneman, Anke, Cupples, L. Adrienne, Booth, Sarah L., Vasan, Ramachandran S., Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G., Shea, M. Kyla, Houston, Denise K., Kritchevsky, Stephen B., Liu, Yongmei, Lohman, Kurt K., Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E., März, Winfried, de Boer, Ian H., Wood, Alexis C., Rotter, Jerome I., Rich, Stephen S., Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K., Wilson, James F., Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M. Carola, Uitterlinden, Andre G., Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M., Timofeeva, Maria, Dunlop, Malcolm G., Valdes, Ana M., Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T., Mikkilä, Vera, Ikram, M. Arfan, Sattar, Naveed, Jukema, J. Wouter, Wareham, Nicholas J., Langenberg, Claudia, Forouhi, Nita G., Gundersen, Thomas E., Khaw, Kay-Tee, Butterworth, Adam S., Danesh, John, Spector, Timothy, Wang, Thomas J., Hyppönen, Elina, Kraft, Peter and Kiel, Douglas P. (2018) Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9 (1). 260/1-260/11. ISSN 2041-1723

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Rheumatology, Orthopaedics and Dermatology
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Depositing User: Eprints, Support
Date Deposited: 01 Feb 2018 15:45
Last Modified: 04 May 2020 19:27

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