학술논문
Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Document Type
article
Author
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 CPGM 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
Source
Nature Communications. 9(1)
Subject
Language
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.