Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Journal article
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, ... Lorentzon, Mattias. (2018). Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications. 9(1), p. 260. https://doi.org/10.1038/s41467-017-02662-2
Authors | 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. and Lorentzon, Mattias |
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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. |
Year | 2018 |
Journal | Nature Communications |
Journal citation | 9 (1), p. 260 |
Publisher | Nature Publishing Group |
ISSN | 2041-1723 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41467-017-02662-2 |
Scopus EID | 2-s2.0-85041401774 |
Open access | Open access |
Page range | 1-12 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | License |
Output status | Published |
Publication dates | |
Online | 17 Jan 2018 |
Publication process dates | |
Accepted | 15 Dec 2017 |
Additional information | Please refer to the full article for a complete list of author names. |
Place of publication | United Kingdom |
https://acuresearchbank.acu.edu.au/item/86q32/genome-wide-association-study-in-79-366-european-ancestry-individuals-informs-the-genetic-architecture-of-25-hydroxyvitamin-d-levels
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