Metaanálisis2010
Common genetic determinants of vitamin D insufficiency: a genome-wide association study
Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O'Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung CL, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen AL, Zhai G, Macdonald HM, Forouhi NG, Loos RJ, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jansson JO, Cauley JA, Uitterlinden AG, Gibson Q, Järvelin MR, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hyppönen E, Spector TD
Lancet (London, England) · 1,219 citas
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- National Institute on Aging (N01‐AG‐6–2101); National Heart, Lung, and Blood Institute (N01-HC-85081); European Commission (QLG2-CT-2002-01254); National Institutes of Health (N01-AG-6-2103); Wellcome Trust (068545/Z/02)); Wellcome Trust (FP7/2007–2013); National Heart, Lung, and Blood Institute (N01 HC085086); National Heart, Lung, and Blood Institute (N01HC-85083); National Institute on Aging (R01 AG014759); National Heart, Lung, and Blood Institute (R01-HL-087652); National Institutes of Health (R01 AR/AG 41398); National Center for Research Resources (M01-RR 00750); National Institute of Diabetes and Digestive and Kidney Diseases (DK063491); Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810); American Heart Association (N01-HC-25195); National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK033651); National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR46838); National Heart, Lung, and Blood Institute (5R01 HL087679-02); National Heart, Lung, and Blood Institute (068545/Z/02); 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Nederlandse Organisatie voor Wetenschappelijk Onderzoek (911-03-012); National Heart, Lung, and Blood Institute (N01AG62101); National Institute for Health and Care Research (PHCS/C4/4/016); European Commission (FP7 2007-2013); National Heart, Lung, and Blood Institute (N01 HC015103); National Institute of Diabetes and Digestive and Kidney Diseases (DK062418); National Heart, Lung, and Blood Institute (N01 HC55222); European Commission (200800); National Institute on Aging (AG 14759); National Institute of Mental Health (RL1-MH083268); National Heart, Lung, and Blood Institute (N01 HC085085); European Commission (201413); Wellcome Trust (G0600705); European Commission (201865); National Institute of Mental Health (1RL1MH083268-01); Nederlandse Organisatie voor Wetenschappelijk Onderzoek (175.010.200); National Institute on Aging (R01AG041517); National Heart, Lung, and Blood Institute (R01 HL087679); National Heart, Lung, and Blood Institute (N01-HC-025195); National Heart, Lung, and Blood Institute (R01 HL084443); National Institute for Health and Care Research (NF-SI-0508-10082); National Heart, Lung, and Blood Institute (N01AG62106); National Institute for Health and Care Research (NF-SI-0508-10275); Nederlandse Organisatie voor Wetenschappelijk Onderzoek (175.010.2005.011); Medical Research Council (068545/Z/02); Medical Research Council (G0000934); Wellcome Trust (068545); National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK062418); European Commission (FP7/2007); U.S. Department of Agriculture (58-1950-7-707); National Institutes of Health (N01-AG-6-2101); National Heart, Lung, and Blood Institute (N01HC085082); National Institute on Aging (P01AG18397); Medical Research Council (grant G0600705); National Institute on Aging (N01 AG062106); National Heart, Lung, and Blood Institute (U01HL080295); European Commission (01254); National Heart, Lung, and Blood Institute (N01 HC055222); National Heart, Lung, and Blood Institute (N01AG62103); National Heart, Lung, and Blood Institute (1RL1MH083268-01); Medical Research Council (G0600705); National Institutes of Health (068545/Z/02); National Institute on Aging (N01AG62106); Juvenile Diabetes Research Foundation International (068545/Z/02); National Institutes of Health (n01hc025195-11-0-0); Wellcome Trust (079895); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488); National Institutes of Health (HHSN268200782096C); National Heart, Lung, and Blood Institute (N01 HC085081); Academy of Finland (120315); National Heart, Lung, and Blood Institute (G0000934); Oulun Yliopisto (FP7/2007-2013); National Institute on Aging (R01 AG-027002); National Human Genome Research Institute (U01 DK062418); National Heart, Lung, and Blood Institute (N01 HC075150); School of Medicine, Boston University (N01-HC25195); Agricultural Research Service (581950-7-707); National Human Genome Research Institute (HHSN268200782096C); Academy of Finland (104781); National Heart, Lung, and Blood Institute (N01 HC085084); ZonMw (050-060-810); National Heart, Lung, and Blood Institute (N01 HC045133); National Institute on Aging (N01-AG-62103); Biotechnology and Biological Sciences Research Council (G20234); National Institute on Aging (N01 AG062103); Medical Research Council (HHSN268200782096C); Erasmus Medisch Centrum (014-93-015); National Institute on Aging (P01AG018397); Wellcome Trust (076113); National Institutes of Health (R01 AR46838); National Institutes of Health (U01 DK062418); National Institutes of Health (N01-HC 25195); National Institutes of Health (AG14759); National Heart, Lung, and Blood Institute (N01-HC85079); National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR041398)); National Institute on Aging (N01 AG062101)
Según 46 financiadores declarados.
Publicación
- Publicado
- 2010-06-11 · Lancet · vol. 376 · número 9736 · págs. 180–188
- Editorial
- Elsevier BV
- Citado
- 1,540 citas · más que el 100% de estudios similares · 73.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 37 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Vitamin D Research Studies · Genetic Associations and Epidemiology · Nutrition, Genetics, and Disease
- Palabras clave
- vitamin D insufficiency, 25-hydroxyvitamin D, genetic factors, vitamin D metabolism, GC gene, DHCR7, CYP2R1, CYP24A1, genetic variants, genotype score, heritability, European ancestry, vitamin D supplementation, sun exposure, diet, bone health
- MeSH
- chromosomes, human, pair 4, chromosomes, human, pair 11, humans, vitamin d deficiency, genetic predisposition to disease, vitamin d, immunoassay, cohort studies, seasons, heterozygote, homozygote, linkage disequilibrium, polymorphism, single nucleotide, international cooperation, dietary supplements, canada, united states, europe, genome-wide association study, white people
76 autores
- Thomas J. Wang🇺🇸 · autor de correspondenciaHarvard University; Massachusetts General Hospital; Framingham Heart Study
- Feng Zhang🇬🇧King's College London
- John Brent Richards🇨🇦Jewish General Hospital; McGill University
- Bryan R. Kestenbaum🇺🇸Harborview Medical Center
- Joyce B. J. van Meurs🇳🇱Erasmus MC; Netherlands Consortium for Healthy Ageing
- Diane J. Berry🇬🇧University College London
- Douglas P. Kiel🇺🇸Framingham Heart Study; Hebrew SeniorLife
- Elizabeth A. Streeten🇺🇸University of Maryland, Baltimore
- Claes Ohlsson🇸🇪University of Gothenburg
- Daniel L. Koller🇺🇸Indiana University Indianapolis; Indiana University School of Medicine
- Leena Peltonen🇫🇮🇬🇧University of Helsinki; Wellcome Sanger Institute; Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland
- Jason D. Cooper🇬🇧University of Cambridge
- Paul F. O’Reilly🇬🇧Imperial College London
- Denise K. Houston🇺🇸Wake Forest University Health Sciences; Wake Forest University
- Nicole L. Glazer🇺🇸University of Washington
- Liesbeth Vandenput🇸🇪University of Gothenburg
- Munro Peacock🇺🇸Indiana University Indianapolis; Indiana University School of Medicine
- Julia M. Shi🇺🇸University of Maryland, Baltimore
- Fernando Rivadeneira🇳🇱Erasmus MC; Netherlands Consortium for Healthy Ageing
- Mark I. McCarthy🇬🇧Centre for Human Genetics; Churchill Hospital; University of Oxford; Oxford Centre for Diabetes, Endocrinology and Metabolism
- Anneli Pouta🇫🇮Finnish Institute for Health and Welfare
- Ian H. de Boer🇺🇸Harborview Medical Center
- Massimo Mangino🇬🇧King's College London
- Bernet Sekasanvu Kato🇬🇧King's College London
- Deborah J. Smyth🇬🇧University of Cambridge
- Sarah L. Booth🇺🇸Tufts University; Jean Mayer Human Nutrition Research Center on Aging
- Paul F. Jacques🇺🇸Tufts University; Jean Mayer Human Nutrition Research Center on Aging
- Greg L. Burke🇺🇸Wake Forest University
- Mark O. Goodarzi🇺🇸Cedars-Sinai Medical Center
- Ching‐Lung Cheung🇸🇬🇺🇸Agency for Science, Technology and Research; Hebrew SeniorLife; Genome Institute of Singapore
- Myles Selig Wolf🇺🇸University of Miami
- Kenneth M. Rice🇺🇸University of Washington
- David Goltzman🇨🇦McGill University Health Centre; McGill University
- Nick Hidiroglou🇨🇦Health Canada
- Martin Ladouceur🇨🇦Jewish General Hospital; McGill University
- Nicholas J. Wareham🇬🇧Addenbrooke's Hospital; MRC Epidemiology Unit
- Lynne J. Hocking🇬🇧University of Aberdeen
- Deborah J Hart🇬🇧King's College London
- Nigel Arden🇬🇧University of Oxford; University of Southampton
- Cyrus C. Cooper🇬🇧University of Oxford; University of Southampton
- Suneil Malik🇨🇦Public Health Agency of Canada
- William Duncan Fraser🇬🇧University of Liverpool
- Anna‐Liisa Hartikainen🇫🇮University of Oulu
- Guangju Zhai🇬🇧King's College London
- Helen M. Macdonald🇬🇧University of Aberdeen
- Nita G. Forouhi🇬🇧Addenbrooke's Hospital; MRC Epidemiology Unit
- Ruth J. F. Loos🇬🇧Addenbrooke's Hospital; MRC Epidemiology Unit
- David M. Reid🇬🇧University of Aberdeen
- Alan J. Hakim🇬🇧Whipps Cross University Hospital
- Elaine Margaret Dennison🇬🇧University of Southampton
- Yongmei Liu🇺🇸Wake Forest University Health Sciences; Wake Forest University
- Chris Power🇬🇧University College London
- Helen E. Stevens🇬🇧University of Cambridge
- Jaana Laitinen🇫🇮Finnish Institute of Occupational Health; University of Oulu
- Ramachandran Srini Vasan🇺🇸Boston University; Framingham Heart Study
- Nicole Soranzo🇬🇧King's College London; Wellcome Sanger Institute
- Jörg Bojunga🇩🇪Goethe University Frankfurt; University Hospital Frankfurt
- Bruce M. Psaty🇺🇸University of Washington
- Mattias Lorentzon🇸🇪University of Gothenburg
- Tatiana Foroud🇺🇸Indiana University Indianapolis; Indiana University School of Medicine
- Tamara B. Harris🇺🇸National Institutes of Health; National Institute on Aging
- Albert Hofman D🇳🇱Erasmus MC; Netherlands Consortium for Healthy Ageing
- John‐Olov Jansson🇸🇪University of Gothenburg
- Jane A. Cauley🇺🇸University of Pittsburgh
- André Gerardus Uitterlinden🇳🇱Erasmus MC; Netherlands Consortium for Healthy Ageing
- Quince Gibson🇳🇱Erasmus MC
- Marjo‐Riitta Järvelin🇫🇮🇬🇧Finnish Institute for Health and Welfare; Imperial College London; University of Oulu
- David Karasik🇺🇸Hebrew SeniorLife
- David S. Siscovick🇺🇸University of Washington
- Michael J. Econs🇺🇸Indiana University Indianapolis; Indiana University School of Medicine
- Stephen B. Kritchevsky🇺🇸Wake Forest University Health Sciences; Wake Forest University
- José C. Florez🇺🇸Broad Institute; Harvard University; Massachusetts General Hospital
- John A. Todd🇬🇧University of Cambridge
- Josée Dupuis🇺🇸Boston University; Framingham Heart Study
- Elina Hyppönen🇬🇧 · autor de correspondenciaUniversity College London
- Tim D. Spector🇬🇧 · autor de correspondenciaKing's College London
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.
Methods
We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants.
Findings
Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile.
Interpretation
Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency.
Funding
Full funding sources listed at end of paper (see Acknowledgments).
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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