Funded in part by Novo Nordisk Fonden
Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Jiang X, O'Reilly PF, Aschard H, Aschard H, Hsu YH, Richards JB, Dupuis J, Ingelsson E, Karasik D, Pilz S, Berry D, Kestenbaum B, Zheng J, Luan J, Sofianopoulou E, Streeten EA, Albanes D, Lutsey PL, Yao L, Tang W, Econs MJ, Wallaschofski H, Völzke H, Zhou A, Power C, McCarthy MI, Michos ED, Boerwinkle E, Weinstein SJ, Freedman ND, Huang WY, Van Schoor NM, van der Velde N, Groot LCPGM, Enneman A, Cupples LA, Booth SL, Vasan RS, Liu CT, Zhou Y, Ripatti S, Ohlsson C, Vandenput L, Lorentzon M, Eriksson JG, Shea MK, Houston DK, Kritchevsky SB, Liu Y, Lohman KK, Ferrucci L, Peacock M, Gieger C, Beekman M, Slagboom E, Deelen J, Heemst DV, Kleber ME, März W, de Boer IH, Wood AC, Rotter JI, Rich SS, Robinson-Cohen C, den Heijer M, Jarvelin MR, Cavadino A, Joshi PK, Wilson JF, Hayward C, Lind L, Michaëlsson K, Trompet S, Zillikens MC, Uitterlinden AG, Rivadeneira F, Broer L, Zgaga L, Campbell H, Theodoratou E, Farrington SM, Timofeeva M, Dunlop MG, Valdes AM, Tikkanen E, Lehtimäki T, Lyytikäinen LP, Kähönen M, Raitakari OT, Mikkilä V, Ikram MA, Sattar N, Jukema JW, Wareham NJ, Langenberg C, Forouhi NG, Gundersen TE, Khaw KT, Butterworth AS, Danesh J, Spector T, Wang TJ, Hyppönen E, Kraft P, Kiel DP
Nature communications · 332 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Cohort study (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Industry funded
- Nonprofit
- Wellcome Trust
- Nonprofit
- Cancer Research UK
- Government
- National Institute for Health and Care Research
- Nonprofit
- British Heart Foundation
- Company
- Novo Nordisk Fonden
- Government
- Medical Research Council
- Government
- Economic and Social Research Council
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Government
- National Center for Advancing Translational Sciences
- Government
- National Institute for Health Research (NIHR)
- Government
- NCATS NIH HHS
- Government
- NIAMS NIH HHS
- Government
- NIDDK NIH HHS
- Grants
- Novo Nordisk Fonden (NNF14OC0010513); National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR072199); National Institute for Health and Care Research (NF-SI-0512-10165); Medical Research Council (MC_UU_12015/5); National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK063491); National Center for Advancing Translational Sciences (UL1TR001881.); Medical Research Council (MR/N01104X/1); Cancer Research UK (18927); Novo Nordisk Fonden (NNF13OC0005785); Medical Research Council (MC_PC_13048); National Institute for Health and Care Research (PHCS/C4/4/016); Medical Research Council (MR/L003120/1); Medical Research Council (MC_UU_00007/1); British Heart Foundation (PG/09/023/26806); Medical Research Council (MR/N01104X/2); Medical Research Council (MR/N015746/1); National Institute for Health and Care Research (NF-SI-0611-10099); Cancer Research UK (14136); Novo Nordisk Fonden (NNF17OC0026882); National Institute for Health and Care Research (NF-SI-0512-10114); Medical Research Council (MR/N003284/1); Wellcome Trust (213422/Z/18/Z); Medical Research Council (MC_UU_12015/1); Economic and Social Research Council (ES/S008349/1); Cancer Research UK (12076); National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK109019); Medical Research Council (MC_UU_00007/10); British Heart Foundation (RG/08/014/24067); Medical Research Council (MR/K018647/1); National Institute for Health and Care Research (NF-SI-0512-10135); National Institute for Health and Care Research (NF-SI-0617-10149); Economic and Social Research Council (ES/S008349/1); Cancer Research UK (22804); National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR041398))
Based on 14 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-01-11 · Nat Commun · vol. 9 · issue 1 · p. 260
- Publisher
- Nature Portfolio
- Cited
- 408 citations · more than 100% of similar papers · 29.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 58 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Vitamin D Research Studies · Genetic Associations and Epidemiology · Epigenetics and DNA Methylation
- Keywords
- Genome-wide association study, Biology, Single-nucleotide polymorphism, Genetic architecture, Vitamin D and neurology, Genetic association, Genetics, Heritability, CYP24A1, Genome, Linkage disequilibrium, Gene, Quantitative trait locus, Calcitriol receptor, Genotype, Endocrinology
- MeSH
- humans, autoimmune diseases, amidohydrolases, vitamin d, vesicular transport proteins, cohort studies, polymorphism, single nucleotide, female, male, genome-wide association study, white people
100 authors
From US, SE, GB, FR, AT, DE, AU, NL, FI, IE, NO
- Xia JiangHarvard University; Karolinska Institutet
- Paul F. O’ReillyKing's College London
- Hugues AschardHarvard University; Institut Pasteur
- Yi-Hsiang HsuBroad Institute; Beth Israel Deaconess Medical Center; Harvard University; Hebrew SeniorLife; Massachusetts Institute of Technology
- John Brent Richards
- Josée DupuisBoston University; Framingham Heart Study
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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