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 · 333 citas

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Cómo se estudió

Diseño: Estudio de cohortes (indexado por PubMed)
Estudiado en: Personas
Resultado principal: Marcadores de salud y funcionamiento

Quién lo pagó

Financiación: Financiado por la industria
Organización sin fines de lucro: Wellcome Trust
Organización sin fines de lucro: Cancer Research UK
Gobierno: National Institute for Health and Care Research
Organización sin fines de lucro: British Heart Foundation
Empresa: Novo Nordisk Fonden
Gobierno: Medical Research Council
Gobierno: Economic and Social Research Council
Gobierno: National Institute of Diabetes and Digestive and Kidney Diseases
Gobierno: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Gobierno: National Center for Advancing Translational Sciences
Gobierno: National Institute for Health Research (NIHR)
Gobierno: NCATS NIH HHS
Gobierno: NIAMS NIH HHS
Gobierno: NIDDK NIH HHS
Subvenciones: 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))

Según 14 financiadores declarados y la declaración de financiación del texto completo.

Publicación

Publicado: 2018-01-11 · Nat Commun · vol. 9 · número 1 · pág. 260
Editorial: Nature Portfolio
Citado: 408 citas · más que el 100% de estudios similares · 29.9× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 58 trabajos
Acceso: Acceso abierto (revista) · CC-BY
Áreas de investigación: Vitamin D Research Studies · Genetic Associations and Epidemiology · Epigenetics and DNA Methylation
Palabras clave: 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

DOI ↗PubMed Central ↗OpenAlex ↗

100 autores

Xia Jiang🇺🇸🇸🇪Harvard University; Karolinska Institutet
Paul F. O’Reilly🇬🇧King's College London
Hugues Aschard🇺🇸🇫🇷Harvard University; Institut Pasteur
Yi-Hsiang Hsu🇺🇸Broad Institute; Beth Israel Deaconess Medical Center; Harvard University; Hebrew SeniorLife; Massachusetts Institute of Technology
John Brent Richards
Josée Dupuis🇺🇸Boston University; Framingham Heart Study
Erik Ingelsson🇸🇪🇺🇸Uppsala University; Stanford University
David Karasik🇺🇸Hebrew SeniorLife
Stefan Pilz🇦🇹Medical University of Graz
Diane J. Berry🇬🇧University College London
Bryan R. Kestenbaum
Ju‐Sheng Zheng🇬🇧University of Cambridge; MRC Epidemiology Unit
Jian’an Luan🇬🇧University of Cambridge; MRC Epidemiology Unit
Eleni Sofianopoulou🇬🇧University of Cambridge
Elizabeth A. Streeten🇺🇸University of Maryland, Baltimore
Demetrius Albanes🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Pamela L. Lutsey🇺🇸University of Minnesota
Lu Yao🇺🇸University of Minnesota
Weihong Tang🇺🇸University of Minnesota
Michael J. Econs🇺🇸Indiana University – Purdue University Indianapolis
Henri Wallaschofski🇩🇪Universitätsmedizin Greifswald; German Centre for Cardiovascular Research
Henry Völzke🇩🇪Universitätsmedizin Greifswald; German Centre for Cardiovascular Research
Ang Zhou🇦🇺University of South Australia
Chris Power🇬🇧University College London
Mark I. McCarthy🇬🇧Centre for Human Genetics; Churchill Hospital; University of Oxford; Oxford Centre for Diabetes, Endocrinology and Metabolism
Erin D. Michos🇺🇸Johns Hopkins University
Eric Boerwinkle🇺🇸The University of Texas Health Science Center at Houston
Stephanie J. Weinstein🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Neal D. Freedman🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Wen‐Yi Huang🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
Natasja M. van Schoor🇳🇱Amsterdam UMC Location Vrije Universiteit Amsterdam
Nathalie van der Velde🇳🇱Erasmus MC; University of Amsterdam; Erasmus University Rotterdam
C.P.G.M. de Groot🇳🇱Wageningen University & Research
Anke W. Enneman🇳🇱Erasmus MC; Erasmus University Rotterdam
L. Adrienne Cupples🇺🇸Boston University; Framingham Heart Study
Sarah L. Booth🇺🇸Tufts University; Jean Mayer Human Nutrition Research Center on Aging
Ramachandran Srini Vasan🇺🇸Framingham Heart Study
Ching‐Ti Liu🇺🇸Boston University
Yanhua Zhou🇺🇸Boston University
Samuli Ripatti🇫🇮University of Helsinki
Claes Ohlsson🇸🇪University of Gothenburg
Liesbeth Vandenput🇸🇪University of Gothenburg
Mattias Lorentzon🇸🇪Sahlgrenska University Hospital; University of Gothenburg
Johan Gunnar Eriksson🇫🇮University of Helsinki; Helsinki University Hospital; Folkhälsans Forskningscentrum
M. Kyla Shea🇺🇸Tufts University; Jean Mayer Human Nutrition Research Center on Aging
Denise K. Houston🇺🇸Wake Forest University
Stephen B. Kritchevsky🇺🇸Wake Forest University
Ching‐Ti Liu🇺🇸Wake Forest University
Kurt K. Lohman🇺🇸Wake Forest University
Luigi Ferrucci🇺🇸National Institute on Aging
Munro Peacock🇺🇸Indiana University – Purdue University Indianapolis
Christian Gieger🇩🇪Helmholtz Munich
Marian Beekman🇳🇱Leiden University Medical Center
P. Eline Slagboom🇳🇱Leiden University Medical Center
Joris Deelen🇳🇱🇩🇪Leiden University Medical Center; Max Planck Institute for Biology of Ageing
Diana van Heemst🇳🇱Leiden University Medical Center
Marcus Edi Kleber🇩🇪Heidelberg University; University Hospital Heidelberg; University Medical Centre Mannheim
Winfried März🇦🇹🇩🇪Medical University of Graz; Heidelberg University; University Hospital Heidelberg; Synlab (Germany); University Medical Centre Mannheim
Ian H. de Boer🇺🇸University of Washington
Alexis C. Wood🇺🇸Children's Nutrition Research Center at Baylor College of Medicine
Jerome I. Rotter🇺🇸The Lundquist Institute; Harbor–UCLA Medical Center
Stephen S. Rich🇺🇸University of Virginia
Cassianne Robinson‐Cohen🇺🇸Vanderbilt University Medical Center
Martin den Heijer🇳🇱Erasmus MC; Erasmus University Rotterdam
Marjo‐Riitta Järvelin🇫🇮🇬🇧Oulu University Hospital; Biocenter Finland; Imperial College London; University of Oulu
Alana Cavadino🇬🇧Queen Mary University of London; University College London
Peter K. Joshi🇬🇧University of Edinburgh
James Fox Wilson🇬🇧Western General Hospital; Institute of Genetics and Cancer; University of Edinburgh
Caroline Hayward🇬🇧Western General Hospital; Institute of Genetics and Cancer; University of Edinburgh
Lars Lind🇸🇪Uppsala University
Karl Michaëlsson🇸🇪Uppsala University
Stella Trompet🇳🇱Leiden University Medical Center
M. Carola Zillikens🇳🇱Erasmus MC; Erasmus University Rotterdam
André Gerardus Uitterlinden🇳🇱Erasmus MC; Erasmus University Rotterdam
Fernando Rivadeneira🇳🇱Erasmus MC; Erasmus University Rotterdam
Linda Broer🇳🇱Erasmus MC; Erasmus University Rotterdam
Lina Zgaga🇮🇪Trinity College Dublin
Harry J. Campbell🇬🇧Western General Hospital; University of Edinburgh
Evropi Τheodoratou🇬🇧Western General Hospital; University of Edinburgh
Susan Mary Farrington🇬🇧Western General Hospital; University of Edinburgh
Maria N Timofeeva🇬🇧Western General Hospital; University of Edinburgh
Malcolm G. Dunlop🇬🇧Western General Hospital; University of Edinburgh
Ana Maria Valdes🇬🇧King's College London; Nottingham City Hospital
Emmi Tikkanen🇫🇮University of Helsinki; Finland University; Institute for Molecular Medicine Finland
Terho J. Lehtimäki🇫🇮Tampere University; Fimlab (Finland)
Leo‐Pekka Lyytikäinen🇫🇮Tampere University; Fimlab (Finland)
Mika A. P. Kähönen🇫🇮Tampere University Hospital; Tampere University
Olli Tuomas Raitakari🇫🇮University of Turku; Turku University Hospital
Vera Mikkilä🇫🇮Research Council of Finland
M. Arfan Ikram🇳🇱Erasmus MC; Erasmus University Rotterdam
Naveed A. Sattar
J. Wouter Jukema🇳🇱Leiden University Medical Center
Nicholas J. Wareham🇬🇧University of Cambridge; MRC Epidemiology Unit
Claudia Langenberg🇬🇧University of Cambridge; MRC Epidemiology Unit
Nita G. Forouhi🇬🇧University of Cambridge; MRC Epidemiology Unit
Thomas E. Gundersen🇳🇴Vitas (Norway)
Kay‐Tee Khaw🇬🇧University of Cambridge
Adam S. Butterworth🇬🇧University of Cambridge
John Danesh🇬🇧University of Cambridge; Wellcome Sanger Institute
Timothy D. Spector🇬🇧King's College London

Resumen

El texto original del estudio, en el idioma en que se publicó.

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.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

Leer el texto completo ↗Ver en PubMed ↗

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