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

Publication ,  Journal Article
Jiang, X; O'Reilly, PF; Aschard, H; Hsu, Y-H; Richards, JB; Dupuis, J; Ingelsson, E; Karasik, D; Pilz, S; Berry, D; Kestenbaum, B; Zheng, J ...
Published in: Nat Commun
January 17, 2018

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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 17, 2018

Volume

9

Issue

1

Start / End Page

260

Location

England

Related Subject Headings

  • White People
  • Vitamin D
  • Vesicular Transport Proteins
  • Polymorphism, Single Nucleotide
  • Male
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cohort Studies
  • Autoimmune Diseases
 

Citation

APA
Chicago
ICMJE
MLA
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Jiang, 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. Nat Commun, 9(1), 260. https://doi.org/10.1038/s41467-017-02662-2
Jiang, Xia, Paul F. O’Reilly, Hugues Aschard, Yi-Hsiang Hsu, J Brent Richards, Josée Dupuis, Erik Ingelsson, et al. “Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.Nat Commun 9, no. 1 (January 17, 2018): 260. https://doi.org/10.1038/s41467-017-02662-2.
Jiang X, O’Reilly PF, Aschard H, Hsu Y-H, Richards JB, Dupuis J, et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun. 2018 Jan 17;9(1):260.
Jiang, Xia, et al. “Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.Nat Commun, vol. 9, no. 1, Jan. 2018, p. 260. Pubmed, doi:10.1038/s41467-017-02662-2.
Jiang X, O’Reilly PF, Aschard H, Hsu Y-H, Richards JB, 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, Groot LCPGMD, Enneman A, Cupples LA, Booth SL, Vasan RS, Liu C-T, Zhou Y, Ripatti S, Ohlsson C, Vandenput L, Lorentzon M, Eriksson JG, Shea MK, Houston DK, Kritchevsky SB, Liu Y, Lohman KK, Ferrucci L, Peacock M, Gieger C, Beekman M, Slagboom E, Deelen J, Heemst DV, Kleber ME, März W, de Boer IH, Wood AC, Rotter JI, Rich SS, Robinson-Cohen C, den Heijer M, Jarvelin M-R, Cavadino A, Joshi PK, Wilson JF, Hayward C, Lind L, Michaëlsson K, Trompet S, Zillikens MC, 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 MA, Sattar N, Jukema JW, 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. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun. 2018 Jan 17;9(1):260.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 17, 2018

Volume

9

Issue

1

Start / End Page

260

Location

England

Related Subject Headings

  • White People
  • Vitamin D
  • Vesicular Transport Proteins
  • Polymorphism, Single Nucleotide
  • Male
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cohort Studies
  • Autoimmune Diseases