Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Xia JiangPaul F O'ReillyHugues AschardYi-Hsiang HsuJohn Brent RichardsJosée DupuisErik IngelssonDavid KarasikStefan PilzDiane BerryBryan KestenbaumJusheng ZhengJianan LuanEleni SofianopoulouElizabeth A StreetenDemetrius AlbanesPamela L LutseyLu YaoWeihong TangMichael J EconsHenri WallaschofskiHenry VölzkeAng ZhouChris PowerMark I McCarthyErin D MichosEric BoerwinkleStephanie J WeinsteinNeal D FreedmanWen-Yi HuangNatasja M Van SchoorNathalie van der VeldeLisette C P G M de GrootAnke EnnemanL Adrienne CupplesSarah L BoothRamachandran S VasanChing-Ti LiuYanhua ZhouSamuli RipattiClaes OhlssonLiesbeth VandenputMattias LorentzonJohan G ErikssonM Kyla SheaDenise K HoustonStephen B KritchevskyYongmei LiuKurt K LohmanLuigi FerrucciMunro PeacockChristian GiegerMarian BeekmanEline SlagboomJoris DeelenDiana van HeemstMarcus Edi KleberWinfried MärzIan H de BoerAlexis C WoodJerome I RotterStephen S RichCassianne Robinson-CohenMartin den HeijerMarjo-Riitta JarvelinAlana CavadinoPeter K JoshiJames F WilsonCaroline HaywardLars LindKarl MichaëlssonStella TrompetM Carola ZillikensAndre G UitterlindenFernando RivadeneiraLinda BroerLina ZgagaHarry CampbellEvropi TheodoratouSusan M FarringtonMaria TimofeevaMalcolm G DunlopAna M ValdesEmmi TikkanenTerho LehtimäkiLeo-Pekka LyytikainenMika KähönenOlli T RaitakariVera MikkiläMohammad Arfan IkramNaveed SattarJohan Wouter JukemaNicholas J WarehamClaudia LangenbergNita G ForouhiThomas E GundersenKay-Tee KhawAdam S ButterworthJohn DaneshTimothy SpectorThomas J WangElina HyppönenPeter KraftDouglas P KielPublished in: Nature communications (2018)
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.