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

Nat Commun
Authors
Xia Jiang
Paul O'Reilly
Hugues Aschard
Yi-Hsiang Hsu
J Brent Richards
Josée Dupuis
Erik Ingelsson
David Karasik
Stefan Pilz
Diane Berry
Bryan Kestenbaum
Jusheng Zheng
Jianan Luan
Eleni Sofianopoulou
Elizabeth Streeten
Demetrius Albanes
Pamela Lutsey
Lu Yao
Weihong Tang
Michael Econs
Henri Wallaschofski
Henry Völzke
Ang Zhou
Chris Power
Mark McCarthy
Erin Michos
Eric Boerwinkle
Stephanie Weinstein
Neal Freedman
Wen-Yi Huang
Natasja van Schoor
Nathalie van der Velde
Lisette de Groot
Anke Enneman
L Adrienne Cupples
Sarah Booth
Ramachandran Vasan
Ching-Ti Liu
Yanhua Zhou
Samuli Ripatti
Claes Ohlsson
Liesbeth Vandenput
Mattias Lorentzon
Johan Eriksson
M Kyla Shea
Denise Houston
Stephen Kritchevsky
Yongmei Liu
Kurt Lohman
Luigi Ferrucci
Munro Peacock
Christian Gieger
Marian Beekman
Eline Slagboom
Joris Deelen
Diana van Heemst
Marcus Kleber
Winfried März
Ian de Boer
Alexis Wood
Jerome Rotter
Stephen Rich
Cassianne Robinson-Cohen
Martin Heijer
Marjo-Riitta Jarvelin
Alana Cavadino
Peter Joshi
James Wilson
Caroline Hayward
Lars Lind
Karl Michaëlsson
Stella Trompet
M Carola Zillikens
André Uitterlinden
Fernando Rivadeneira
Linda Broer
Lina Zgaga
Harry Campbell
Evropi Theodoratou
Susan Farrington
Maria Timofeeva
Malcolm Dunlop
Ana Valdes
Emmi Tikkanen
Terho Lehtimäki
Leo-Pekka Lyytikäinen
Mika Kähönen
Olli Raitakari
Vera Mikkilä
M Arfan Ikram
Naveed Sattar
J Wouter Jukema
Nicholas Wareham
Claudia Langenberg
Nita Forouhi
Thomas Gundersen
Kay-Tee Khaw
Adam Butterworth
John Danesh
Timothy Spector
Thomas Wang
Elina Hyppönen
Peter Kraft
Douglas Kiel
Keywords
Female
Humans
Male
Cohort Studies
Genome-Wide Association Study
Polymorphism, Single Nucleotide
European Continental Ancestry Group
Autoimmune Diseases
Amidohydrolases
Vesicular Transport Proteins
Vitamin D
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 = 4.7×10 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.
Year of Publication
2018
Journal
Nat Commun
Volume
9
Issue
1
Pages
260
Date Published
2018 01 17
ISSN
2041-1723
DOI
10.1038/s41467-017-02662-2
PubMed ID
29343764
PubMed Central ID
PMC5772647
Links
Grant list
MC_UU_00007/1 / MRC_ / Medical Research Council / United Kingdom
G1001799 / MRC_ / Medical Research Council / United Kingdom
MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom
MR/N003284/1 / MRC_ / Medical Research Council / United Kingdom
12-1087 / AICR_ / Worldwide Cancer Research / United Kingdom
G1000143 / MRC_ / Medical Research Council / United Kingdom
R01 AR072199 / AR / NIAMS NIH HHS / United States
MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom
G0600329 / MRC_ / Medical Research Council / United Kingdom
MR/N015746/1 / MRC_ / Medical Research Council / United Kingdom
MC_PC_U127527198 / MRC_ / Medical Research Council / United Kingdom
12076 / CRUK_ / Cancer Research UK / United Kingdom
G0601653 / MRC_ / Medical Research Council / United Kingdom
RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom
MR/L003120/1 / MRC_ / Medical Research Council / United Kingdom
R01 AR041398 / AR / NIAMS NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
MC_U127527198 / MRC_ / Medical Research Council / United Kingdom
K01 DK109019 / DK / NIDDK NIH HHS / United States
PHCS/C4/4/016 / DH_ / Department of Health / United Kingdom
14136 / CRUK_ / Cancer Research UK / United Kingdom
G0401527 / MRC_ / Medical Research Council / United Kingdom
MR/K018647/1 / MRC_ / Medical Research Council / United Kingdom
G0600237 / MRC_ / Medical Research Council / United Kingdom
UL1 TR001881 / TR / NCATS NIH HHS / United States
PG/09/023/26806 / BHF_ / British Heart Foundation / United Kingdom

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