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

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dc.contributor.authorJiang, Xia
dc.contributor.authorO’Reilly, Paul F.
dc.contributor.authorAschard, Hugues
dc.contributor.authorHsu, Yi-Hsiang
dc.contributor.authorRichards, J. Brent
dc.contributor.authorDupuis, Josée
dc.contributor.authorIngelsson, Erik
dc.contributor.authorKarasik, David
dc.contributor.authorPilz, Stefan
dc.contributor.authorBerry, Diane
dc.contributor.authorKestenbaum, Bryan
dc.contributor.authorZheng, Jusheng
dc.contributor.authorLuan, Jianan
dc.contributor.authorSofianopoulou, Eleni
dc.contributor.authorStreeten, Elizabeth A.
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorLutsey, Pamela L.
dc.contributor.authorYao, Lu
dc.contributor.authorTang, Weihong
dc.contributor.authorEcons, Michael J.
dc.contributor.authorWallaschofski, Henri
dc.contributor.authorVölzke, Henry
dc.contributor.authorZhou, Ang
dc.contributor.authorPower, Chris
dc.contributor.authorMcCarthy, Mark I.
dc.contributor.authorMichos, Erin D.
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorWeinstein, Stephanie J.
dc.contributor.authorFreedman, Neal D.
dc.contributor.authorHuang, Wen-Yi
dc.contributor.authorVan Schoor, Natasja M.
dc.contributor.authorVelde, Nathalie van der
dc.contributor.authorde Groot, Lisette C. P. G. M.
dc.contributor.authorEnneman, Anke
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorBooth, Sarah L.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorLiu, Ching-Ti
dc.contributor.authorZhou, Yanhua
dc.contributor.authorRipatti, Samuli
dc.contributor.authorOhlsson, Claes
dc.contributor.authorVandenput, Liesbeth
dc.contributor.authorLorentzon, Mattias
dc.contributor.authorEriksson, Johan G.
dc.contributor.authorShea, M. Kyla
dc.contributor.authorHouston, Denise K.
dc.contributor.authorKritchevsky, Stephen B.
dc.contributor.authorLiu, Yongmei
dc.contributor.authorLohman, Kurt K.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorPeacock, Munro
dc.contributor.authorGieger, Christian
dc.contributor.authorBeekman, Marian
dc.contributor.authorSlagboom, Eline
dc.contributor.authorDeelen, Joris
dc.contributor.authorHeemst, Diana van
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorMärz, Winfried
dc.contributor.authorde Boer, Ian H.
dc.contributor.authorWood, Alexis C.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRich, Stephen S.
dc.contributor.authorRobinson-Cohen, Cassianne
dc.contributor.authorHeijer, Martin den
dc.contributor.authorJarvelin, Marjo-Riitta
dc.contributor.authorCavadino, Alana
dc.contributor.authorJoshi, Peter K.
dc.contributor.authorWilson, James F.
dc.contributor.authorHayward, Caroline
dc.contributor.authorLind, Lars
dc.contributor.authorMichaëlsson, Karl
dc.contributor.authorTrompet, Stella
dc.contributor.authorZillikens, M. Carola
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorBroer, Linda
dc.contributor.authorZgaga, Lina
dc.contributor.authorCampbell, Harry
dc.contributor.authorTheodoratou, Evropi
dc.contributor.authorFarrington, Susan M.
dc.contributor.authorTimofeeva, Maria
dc.contributor.authorDunlop, Malcolm G.
dc.contributor.authorValdes, Ana M.
dc.contributor.authorTikkanen, Emmi
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorKähönen, Mika
dc.contributor.authorRaitakari, Olli T.
dc.contributor.authorMikkilä, Vera
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorSattar, Naveed
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorForouhi, Nita G.
dc.contributor.authorGundersen, Thomas E.
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorButterworth, Adam S.
dc.contributor.authorDanesh, John
dc.contributor.authorSpector, Timothy
dc.contributor.authorWang, Thomas J.
dc.contributor.authorHyppönen, Elina
dc.contributor.authorKraft, Peter
dc.contributor.authorKiel, Douglas P.
dc.contributor.departmentMedicine, School of Medicineen_US
dc.date.accessioned2018-05-30T19:43:47Z
dc.date.available2018-05-30T19:43:47Z
dc.date.issued2018-01-17
dc.description.abstractVitamin 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 levelsen_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationJiang, X., O’Reilly, P. F., Aschard, H., Hsu, Y.-H., Richards, J. B., Dupuis, J., … Kiel, D. P. (2018). Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9, 260. http://doi.org/10.1038/s41467-017-02662-2en_US
dc.identifier.urihttps://hdl.handle.net/1805/16303
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/s41467-017-02662-2en_US
dc.relation.journalNature Communicationsen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.sourcePMCen_US
dc.subjectVitamin Den_US
dc.subjectImmunologyen_US
dc.subjectCytokinesen_US
dc.subjectVitamin D in human nutritionen_US
dc.subjectVitamin D in the bodyen_US
dc.subjectVitamin D deficiencyen_US
dc.subjectHuman geneticsen_US
dc.subjectGenetic disordersen_US
dc.subjectMolecular epidemiologyen_US
dc.subjectMeta-analysisen_US
dc.titleGenome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levelsen_US
dc.typeArticleen_US
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