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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Jiang, Xia O'Reilly, Paul F. Aschard, Hugues Hsu, Yi-Hsiang Richards, J. Brent Dupuis, Josée Ingelsson, Erik Karasik, David Pilz, Stefan Berry, Diane
Jiang, Xia
O'Reilly, Paul F.
Aschard, Hugues
Hsu, Yi-Hsiang
Richards, J. Brent
Dupuis, Josée
Ingelsson, Erik
Karasik, David
Pilz, Stefan
Berry, Diane
Author
Jiang, Xia
O'Reilly, Paul F.
Aschard, Hugues
Hsu, Yi-Hsiang
Richards, J. Brent
Dupuis, Josée
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
Völzke, Henry
Zhou, Ang
Power, Chris
McCarthy, Mark I.
Michos, Erin D.
Boerwinkle, Eric
Weinstein, Stephanie J.
Freedman, Neal D.
Lorentzon, Mattias
O'Reilly, Paul F.
Aschard, Hugues
Hsu, Yi-Hsiang
Richards, J. Brent
Dupuis, Josée
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
Völzke, Henry
Zhou, Ang
Power, Chris
McCarthy, Mark I.
Michos, Erin D.
Boerwinkle, Eric
Weinstein, Stephanie J.
Freedman, Neal D.
Lorentzon, Mattias
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 = 4.7×10−9 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.
Keywords
Date
2018
Type
Journal article
Journal
Nature Communications
Book
Volume
9
Issue
1
Page Range
1-12
Article Number
Article 260
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open
Notes
Please refer to the full article for a complete list of author names.