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

Journal article
Authors X. Jiang
P. F. O'Reilly
H. Aschard
Y. H. Hsu
J. B. Richards
J. Dupuis
E. Ingelsson
D. Karasik
S. Pilz
D. Berry
B. Kestenbaum
J. S. Zheng
J. N. Luan
E. Sofianopoulou
E. A. Streeten
D. Albanes
P. L. Lutsey
L. Yao
W. H. Tang
M. J. Econs
H. Wallaschofski
H. Volzke
A. Zhou
C. Power
M. I. McCarthy
E. D. Michos
E. Boerwinkle
S. J. Weinstein
N. D. Freedman
W. Y. Huang
N. M. Van Schoor
N. van der Velde
Lcpgm de Groot
A. Enneman
L. A. Cupples
S. L. Booth
R. S. Vasan
C. T. Liu
Y. H. Zhou
S. Ripatti
Claes Ohlsson
Liesbeth Vandenput
Mattias Lorentzon
J. G. Eriksson
M. K. Shea
D. K. Houston
S. B. Kritchevsky
Y. M. Liu
K. K. Lohman
L. Ferrucci
M. Peacock
C. Gieger
M. Beekman
E. Slagboom
J. Deelen
D. van Heemst
M. E. Kleber
W. Marz
I. H. de Boer
A. C. Wood
J. I. Rotter
S. S. Rich
C. Robinson-Cohen
M. den Heijer
M. R. Jarvelin
A. Cavadino
P. K. Joshi
J. F. Wilson
C. Hayward
L. Lind
K. Michaelsson
S. Trompet
M. C. Zillikens
A. G. Uitterlinden
F. Rivadeneira
L. Broer
L. Zgaga
H. Campbell
E. Theodoratou
S. M. Farrington
M. Timofeeva
M. G. Dunlop
A. M. Valdes
E. Tikkanen
T. Lehtimaki
L. P. Lyytikainen
M. Kahonen
O. T. Raitakari
V. Mikkila
M. A. Ikram
N. Sattar
J. W. Jukema
N. J. Wareham
C. Langenberg
N. G. Forouhi
T. E. Gundersen
K. T. Khaw
A. S. Butterworth
J. Danesh
T. Spector
T. J. Wang
E. Hypponen
P. Kraft
D. P. Kiel
Published in Nature Communications
Volume 9
Issue 1
Pages 260
ISSN 2041-1723
Publication year 2018
Published at Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 260
Language en
Links doi.org/10.1038/s41467-017-02662-2
Keywords vitamin-d levels, lenticulo-sutural dysplasia, partitioning, heritability, multiple-sclerosis, adolescent twins, cell-types, risk, loci, variants, disease, metaanalysis, Science & Technology - Other Topics
Subject categories Public Health, Global Health, Social Medicine and Epidemiology

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.

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