Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
2018
Jiang, Xia | O'Reilly, Paul F. | Aschard, Hugues | Hsu, Yi Hsiang | Richards, J.B. | 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 | Schoor, van, Natasja M. | Velde, van der, Nathalie | Groot, de, Lisette C.P.G.M. | Enneman, Anke | Cupples, L.A. | Booth, Sarah L. | Vasan, Ramachandran S. | Liu, Ching Ti | Zhou, Yanhua | Ripatti, Samuli | Ohlsson, Claes | Vandenput, Liesbeth | Lorentzon, Mattias | Eriksson, Johan G. | Shea, M.K. | Houston, Denise K. | Kritchevsky, Stephen B. | Liu, Yongmei | Lohman, Kurt K. | Ferrucci, Luigi | Peacock, Munro | Gieger, Christian | Beekman, Marian | Slagboom, Eline | Deelen, Joris | Deelen, Joris | Heemst, van, Diana | Kleber, Marcus E. | März, Winfried | Boer, De, Ian H. | Wood, Alexis C. | Rotter, Jerome I. | Rich, Stephen S. | Robinson-Cohen, Cassianne | Heijer, Den, Martin | Jarvelin, Marjo Riitta | Jarvelin, Marjo Riitta | Cavadino, Alana | Cavadino, Alana | Joshi, Peter K. | Wilson, James F. | Hayward, Caroline | Lind, Lars | Michaëlsson, Karl | Trompet, Stella | Zillikens, M.C. | Uitterlinden, Andre G. | Rivadeneira, Fernando
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.
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