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Jiang, X.* ; O'Reilly, P.F.* ; Aschard, H.* ; Hsu, Y.H.* ; Richards, J.B.* ; Dupuis, J.* ; Ingelsson, E.* ; Karasik, D.* ; Pilz, S.* ; Berry, D.* ; Kestenbaum, B.* ; Zheng, J.* ; Luan, J.* ; Sofianopoulou, E.* ; Streeten, E.A.* ; Albanes, D.* ; Lutsey, P.L.* ; Yao, L.* ; Tang, W.* ; Econs, M.J.* ; Wallaschofski, H.* ; Voelzke, H.* ; Zhou, A.* ; Power, C.* ; McCarthy, M.I.* ; Michos, E.D.* ; Boerwinkle, E.* ; Weinstein, S.J.* ; Freedman, N.D.* ; Huang, W.* ; van Schoor, N.M.* ; van der Velde, N.* ; de Groot, L.C.P.G.M.* ; Enneman, A.W.* ; Cupples, L.A.* ; Booth, S.L.* ; Vasan, R.S.* ; Liu, C.* ; Zhou, Y.* ; Ripatti, S.* ; Ohlsson, C.* ; Vandenput, L.* ; Lorentzon, M.* ; Eriksson, J.G.* ; Shea, M.K.* ; Houston, D.K.* ; Kritchevsky, S.B.* ; Liu, Y.* ; Lohman, K.K.* ; Ferrucci, L.* ; Peacock, M.* ; Gieger, C. ; Beekman, M.* ; Slagboom, E.* ; Deelen, J.* ; van Heemst, D.* ; Kleber, M.E.* ; Maerz, W.* ; de Boer, I.H.* ; Wood, A.C.* ; Rotter, J.I.* ; Rich, S.S.* ; Robinson-Cohen, C.* ; den Heijer, M.* ; Jarvelin, M.R.* ; Cavadino, A.* ; Joshi, P.K.* ; Wilson, J.F.* ; Hayward, C.* ; Lind, L.* ; Michaelsson, K.* ; Trompet, S.* ; Zillikens, M.C.* ; Uitterlinden, A.G.* ; Rivadeneira, F.* ; Broer, L.* ; Zgaga, L.* ; Campbell, H.* ; Theodoratou, E.* ; Farrington, S.M.* ; Timofeeva, M.* ; Dunlop, M.G.* ; Valdes, A.M.* ; Tikkanen, E.* ; Lehtimäki, T.* ; Lyytikainen, L.* ; Kähönen, M.* ; Raitakari, O.T.* ; Mikkilä, V.* ; Ikram, M.A.* ; Sattar, N.* ; Jukema, J.W.* ; Wareham, N.J.* ; Langenberg, C.* ; Forouhi, N.G.* ; Gundersen, T.E.* ; Khaw, K.* ; Butterworth, A.S.* ; Danesh, J.* ; Spector, T.* ; Wang, T.J.* ; Hyppönen, E.* ; Kraft, P.* ; Kiel, D.P.*

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

Nat. Commun. 9:260 (2018)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Vitamin-d Levels; Lenticulo-sutural Dysplasia; Partitioning Heritability; Multiple-sclerosis; Adolescent Twins; Cell-types; Risk Loci; Variants; Disease; Metaanalysis
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 260 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-004
DOI 10.1038/s41467-017-02662-2
WOS ID WOS:000422650500011
Scopus ID 85041401774
Erfassungsdatum 2018-03-01
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