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

Jiang, X.; O'Reilly, P. F.; Aschard, H.; Hsu, Y. H.; Richards, J. B.; Dupuis, J.; Ingelsson, E.; Karasik, D.; Pilz, S.; Berry, D.; Kestenbaum, B.; Zheng, J.; Luan, J.; Sofianopoulou, E.; Streeten, E. A.; Albanes, D.; Lutsey, P. L.; Yao, L.; Tang, W.; Econs, M. J.; Wallaschofski, H.; Volzke, H.; Zhou, A.; Power, C.; McCarthy, M. I.; Michos, E. D.; Boerwinkle, E.; Weinstein, S. J.; Freedman, N. D.; Huang, W. Y.; Van Schoor, N. M.; van der Velde, N.; Groot, Lcpgm; Enneman, A.; Cupples, L. A.; Booth, S. L.; Vasan, R. S.; Liu, C. T.; Zhou, Y.; Ripatti, S.; Ohlsson, C.; Vandenput, L.; Lorentzon, M.; Eriksson, J. G.; Shea, M. K.; Houston, D. K.; Kritchevsky, S. B.; Liu, Y.; Lohman, K. K.; Ferrucci, L.; Peacock, M.; Gieger, C.; Beekman, M.; Slagboom, P. E.; Deelen, J.; Heemst, D. V.; Kleber, M. E.; Marz, W.; de Boer, I. H.; Wood, A. C.; Rotter, J. I.; Rich, S. S.; Robinson-Cohen, C.; den Heijer, M.; Jarvelin, M. R.; Cavadino, A.; Joshi, P. K.; Wilson, J. F.; Hayward, C.; Lind, L.; Michaelsson, K.; Trompet, S.; Zillikens, M. C.; Uitterlinden, A. G.; Rivadeneira, F.; Broer, L.; Zgaga, L.; Campbell, H.; Theodoratou, E.; Farrington, S. M.; Timofeeva, M.; Dunlop, M. G.; Valdes, A. M.; Tikkanen, E.; Lehtimaki, T.; Lyytikainen, L. P.; Kahonen, M.; Raitakari, O. T.; Mikkila, V.; Ikram, M. A.; Sattar, N.; Jukema, J. W.; Wareham, N. J.; Langenberg, C.; Forouhi, N. G.; Gundersen, T. E.; Khaw, K. T.; Butterworth, A. S.; Danesh, J.; Spector, T.; Wang, T. J.; Hypponen, E.; Kraft, P.; Kiel, D. P.

doi:10.1038/s41467-017-02662-2

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

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Deelen, J.
Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/29343764
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Citation

Jiang, X., O'Reilly, P. F., Aschard, H., Hsu, Y. H., Richards, J. B., Dupuis, J., et al. (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. doi:10.1038/s41467-017-02662-2.

Cite as: https://hdl.handle.net/21.11116/0000-000B-47D3-7

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.