Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Nature communications 2017 ; 9: 260.
Jiang X, O'Reilly PF, Aschard H, Hsu YH, Richards JB, Dupuis J, Ingelsson E, Karasik D, Pilz S, Zheng JS, Luan J, Streeten EA, Tang W, Econs MJ, Wallaschofski H, Völzke H, Power C, McCarthy MI, Boerwinkle E, van Schoor NM, van der Velde N, Cupples LA, Vasan RS, Liu CT, Zhou Y, Ripatti S, Ohlsson C, Vandenput L, Lorentzon M, Eriksson JG, Houston DK, Kritchevsky SB, Lohman KK, Ferrucci L, Peacock M, Gieger C, Beekman M, Deelen J, Kleber ME, März W, de Boer IH, Rotter JI, Rich SS, Järvelin MR, Cavadino A, Joshi PK, Wilson JF, Hayward C, Lind L, Michaëlsson K, Trompet S, Zillikens MC, Uitterlinden AG, Rivadeneira F, Broer L, Campbell H, Tikkanen E, Lehtimäki T, Lyytikäinen LP, Kähönen M, Raitakari OT, Mikkilä V, Ikram MA, Sattar N, Jukema JW, Wareham NJ, Langenberg C, Forouhi NG, Khaw KT, Butterworth AS, Danesh J, Spector T, Hyppönen E, Kraft P, and Kiel DP
PubMed ID : 29343764
PMCID : PMC5772647
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.