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

Authors:
David Karasik, PhD
David Karasik, PhD
Bar Ilan University
Assoc. Prof.
Boston, MA | United States
Xia Jiang Paul F O'Reilly Hugues Aschard Yi-Hsiang Hsu J Brent Richards Josée Dupuis Erik Ingelsson Stefan Pilz Diane Berry Bryan Kestenbaum Jusheng Zheng Jianan Luan Eleni Sofianopoulou Elizabeth A Streeten Demetrius Albanes Pamela L Lutsey Lu Yao Weihong Tang Michael J Econs Henri Wallaschofski Henry Völzke Ang Zhou Chris Power Mark I McCarthy Erin D Michos Eric Boerwinkle Stephanie J Weinstein Neal D Freedman Wen-Yi Huang Natasja M Van Schoor Nathalie van der Velde Lisette C P G M de Groot Anke Enneman L Adrienne Cupples Sarah L Booth Ramachandran S Vasan Ching-Ti Liu Yanhua Zhou Samuli Ripatti Claes Ohlsson Liesbeth Vandenput Mattias Lorentzon Johan G Eriksson M Kyla Shea Denise K Houston Stephen B Kritchevsky Yongmei Liu Kurt K Lohman Luigi Ferrucci Munro Peacock Christian Gieger Marian Beekman Eline Slagboom Joris Deelen Diana van Heemst Marcus E Kleber Winfried März Ian H de Boer Alexis C Wood Jerome I Rotter Stephen S Rich Cassianne Robinson-Cohen Martin den Heijer Marjo-Riitta Jarvelin Alana Cavadino Peter K Joshi James F Wilson Caroline Hayward Lars Lind Karl Michaëlsson Stella Trompet M Carola Zillikens Andre G Uitterlinden Fernando Rivadeneira Linda Broer Lina Zgaga Harry Campbell Evropi Theodoratou Susan M Farrington Maria Timofeeva Malcolm G Dunlop Ana M Valdes Emmi Tikkanen Terho Lehtimäki Leo-Pekka Lyytikäinen Mika Kähönen Olli T Raitakari Vera Mikkilä M Arfan Ikram Naveed Sattar J Wouter Jukema Nicholas J Wareham Claudia Langenberg Nita G Forouhi Thomas E Gundersen Kay-Tee Khaw Adam S Butterworth John Danesh Timothy Spector Thomas J Wang Elina Hyppönen Peter Kraft Douglas P Kiel

Nat Commun 2018 01 17;9(1):260. Epub 2018 Jan 17.

Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-017-02662-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772647PMC
January 2018
127 Reads
9 Citations
10.742 Impact Factor

Publication Analysis

Top Keywords

25-hydroxyvitamin levels
8
common snps
8
amdhd1 estimate
4
estimate heritability
4
rs10745742 amdhd1
4
p = 19×10 rs10745742
4
heritability 25-hydroxyvitamin
4
sec23a p = 19×10
4
serum concentrations
4
snps 75%
4
75% statistically
4
gwas common
4
attributable gwas
4
rs8018720 sec23a
4
concentrations attributable
4
25-hydroxyvitamin serum
4
p = 47×10 rs8018720
4
16125 79366
4
79366 european
4
european descent
4

References

(Supplied by CrossRef)

LE Mokry et al.
PLoS Med. 2015

B Rhead et al.
Neurol. Genet. 2016

AR Martineau et al.
Br. Med. J. 2017

S Pilz et al.
Nat. Rev. Cardiol. 2016

CF Garland et al.
Am. J. Public Health 2006

DA Fernandes de Abreu et al.
Psychoneuroendocrinology 2009

Z Lagunova et al.
Anticancer Res. 2009

TJ Wang et al.
Lancet Lond. Engl. 2010

C Karohl et al.
Am. J. Clin. Nutr. 2010

SM Orton et al.
Am. J. Clin. Nutr. 2008

J Ahn et al.
Hum. Mol. Genet. 2010

Similar Publications