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

TitleGenome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Publication TypeJournal Article
Year of Publication2018
AuthorsJiang, X, O'Reilly, PF, Aschard, H, Hsu, Y-H, J Richards, B, Dupuis, J, Ingelsson, E, Karasik, D, Pilz, S, Berry, D, Kestenbaum, B, Zheng, J, Luan, J, Sofianopoulou, E, Streeten, EA, Albanes, D, Lutsey, PL, Yao, L, Tang, W, Econs, MJ, Wallaschofski, H, Völzke, H, Zhou, A, Power, C, McCarthy, MI, Michos, ED, Boerwinkle, E, Weinstein, SJ, Freedman, ND, Huang, W-Y, van Schoor, NM, van der Velde, N, de Groot, LCPGM, Enneman, A, Cupples, AL, Booth, SL, Vasan, RS, Liu, C-T, Zhou, Y, Ripatti, S, Ohlsson, C, Vandenput, L, Lorentzon, M, Eriksson, JG, M Shea, K, Houston, DK, Kritchevsky, SB, Liu, Y, Lohman, KK, Ferrucci, L, Peacock, M, Gieger, C, Beekman, M, Slagboom, E, Deelen, J, van Heemst, D, Kleber, ME, März, W, de Boer, IH, Wood, AC, Rotter, JI, Rich, SS, Robinson-Cohen, C, Heijer, Mden, Jarvelin, M-R, Cavadino, A, Joshi, PK, Wilson, JF, Hayward, C, Lind, L, Michaëlsson, K, Trompet, S, Zillikens, CM, Uitterlinden, AG, Rivadeneira, F, Broer, L, Zgaga, L, Campbell, H, Theodoratou, E, Farrington, SM, Timofeeva, M, Dunlop, MG, Valdes, AM, Tikkanen, E, Lehtimäki, T, Lyytikäinen, L-P, Kähönen, M, Raitakari, OT, Mikkilä, V, Ikram, AM, Sattar, N, J Jukema, W, Wareham, NJ, Langenberg, C, Forouhi, NG, Gundersen, TE, Khaw, K-T, Butterworth, AS, Danesh, J, Spector, T, Wang, TJ, Hyppönen, E, Kraft, P, Kiel, DP
JournalNat Commun
Date Published2018 Jan 17
Abstract<p>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 at rs8018720 in SEC23A, and P = 1.9×10 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.</p>
Alternate JournalNat Commun
PubMed ID29343764
PubMed Central IDPMC5772647
Grant ListP30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AR041398 / AR / NIAMS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
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