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

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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-Y , Van Schoor , N M , van der Velde , N , de Groot , L C P G M , Enneman , A , Cupples , L A , Booth , S L , Vasan , R S , Liu , C-T , 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 , Lehtimaki , T , Lyytikainen , L-P , Kahonen , M , Raitakari , O T , Mikkila , V , Ikram , M A , Sattar , N , Jukema , J W , Wareham , N J , Langenberg , C , Forouhi , N G , Gundersen , T E , Khaw , K-T , Butterworth , A S , Danesh , J , Spector , T , Wang , T J , Hypponen , E , Kraft , P & 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 , vol. 9 , 260 . https://doi.org/10.1038/s41467-017-02662-2

Title: Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Author: Jiang, Xia; O'Reilly, Paul F.; Aschard, Hugues; Hsu, Yi-Hsiang; Richards, J. Brent; Dupuis, Josee; 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; Voelzke, 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; de Groot, Lisette C. P. G. M.; 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; van Heemst, Diana; Kleber, Marcus E.; Maerz, 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; Michaelsson, 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; Lehtimaki, Terho; Lyytikainen, Leo-Pekka; Kahonen, Mika; Raitakari, Olli T.; Mikkila, 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; Wang, Thomas J.; Hypponen, Elina; Kraft, Peter; Kiel, Douglas P.
Other contributor: University of Helsinki, Clinicum
University of Helsinki, Department of General Practice and Primary Health Care
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Academy of Finland








Date: 2018-01-17
Language: eng
Number of pages: 12
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-017-02662-2
URI: http://hdl.handle.net/10138/232310
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 = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-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.
Subject: VITAMIN-D LEVELS
LENTICULO-SUTURAL DYSPLASIA
PARTITIONING HERITABILITY
MULTIPLE-SCLEROSIS
ADOLESCENT TWINS
CELL-TYPES
RISK LOCI
VARIANTS
DISEASE
METAANALYSIS
3111 Biomedicine
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