Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Uitterlinden A.; Enneman A.; Van Schoor N.; Dunlop M.; Sattar N.; Michaëlsson K.; Jiang X.; Tikkanen E.; O'Reilly P.; Rotter J.; Lind L.; Hayward C.; Michos E.; Liu Y.; Weinstein S.; McCarthy M.; Van Der Velde N.; Raitakari O.; Cavadino A.; Huang W.; Hsu Y.; Danesh J.; Kiel D.; Slagboom E.; Heemst D.; Robinson-Cohen C.; Pilz S.; Wang T.; Vandenput L.; Zheng J.; Booth S.; Kleber M.; Vasan R.; Cupples L.; Econs M.; Berry D.; Gieger C.; Rich S.; Streeten E.; Freedman N.; Ingelsson E.; Völzke H.; Tang W.; Joshi P.; Yao L.; Theodoratou E.; Kähönen M.; Rivadeneira F.; Hyppönen E.; Valdes A.; Sofianopoulou E.; Kraft P.; Albanes D.; Liu C.; Zgaga L.; Deelen J.; Wallaschofski H.; Campbell H.; Forouhi N.; Zhou A.; Timofeeva M.; Shea M.; Richards J.; Jukema J.; Zhou Y.; Houston D.; Lyytikäinen L.; Mikkilä V.; Ohlsson C.; Lehtimäki T.; Farrington S.; Butterworth A.; Lorentzon M.; Den Heijer M.; Peacock M.; Khaw K.; Luan J.; Ripatti S.; Karasik D.; Power C.; Kestenbaum B.; März W.; Wareham N.; Wilson J.; Kritchevsky S.; Jarvelin M.; Lutsey P.; Eriksson J.; Beekman M.; De Boer I.; Ikram M.; Wood A.; Boerwinkle E.; Lohman K.; Langenberg C.; Zillikens M.; Broer L.; Groot L.; Dupuis J.; Trompet S.; Ferrucci L.; Aschard H.; Spector T.; Gundersen T.
https://urn.fi/URN:NBN:fi-fe2021042718976
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]