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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Jiang, Xia; O'Reilly, Paul F; Aschard, Hugues; Hsu, Yi-Hsiang; Richards, J Brent; Dupuis, Josée; Ingelsson, Erik; Karasik, David; Pilz, Stefan; Berry, Diane; Kestenbaum, Bryan; Zheng, Jusheng; Luan, Jianan; Sofianopoulou, Eleni; Streeten, Elizabeth A; Albanes, Demetrius; Lutsey, Pamela L; Yao, Lu; Tang, Weihong; Econs, Michael J; Wallaschofski, Henri; Völzke, Henry; Zhou, Ang; Power, Chris; McCarthy, Mark I; Michos, Erin D; Boerwinkle, Eric; Weinstein, Stephanie J; Freedman, Neal D; Huang, Wen-Yi; Van Schoor, Natasja M; van der Velde, Nathalie; Groot, Lisette C P G M de; Enneman, Anke; Cupples, L Adrienne; Booth, Sarah L; Vasan, Ramachandran S; Liu, Ching-Ti; Zhou, Yanhua; Ripatti, Samuli; Ohlsson, Claes; Vandenput, Liesbeth; Lorentzon, Mattias; Eriksson, Johan G; Shea, M Kyla; Houston, Denise K; Kritchevsky, Stephen B; Liu, Yongmei; Lohman, Kurt K; Ferrucci, Luigi.
Afiliación
  • Jiang X; Program in Genetic Epidemiology and Statistical Genetics. Department of Epidemiology, Harvard T.H.Chan School of Public Health, 677 Huntington Avenue, Boston, 02115, MA, USA.
  • O'Reilly PF; Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels vagen 13, Stockholm, 17177, Sweden.
  • Aschard H; Department of Social Genetic & Developmental Psychiatry, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK.
  • Hsu YH; Program in Genetic Epidemiology and Statistical Genetics. Department of Epidemiology, Harvard T.H.Chan School of Public Health, 677 Huntington Avenue, Boston, 02115, MA, USA.
  • Richards JB; Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75724, France.
  • Dupuis J; Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.
  • Ingelsson E; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02115, USA.
  • Karasik D; Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA, 02142, USA.
  • Pilz S; Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, 3755 Côte Ste-Catherine Road, Suite H-413 Montréal, Québec, H3T 1E2, Canada.
  • Berry D; Department of Biostatistics, Boston University School of Public Health, Crosstown Center. 801 Massachusetts Avenue 3rd Floor, Boston, MA, 02118, USA.
  • Kestenbaum B; Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.
  • Zheng J; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine Stanford, Stanford, CA, 94305, USA.
  • Luan J; Department of Medical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
  • Sofianopoulou E; Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.
  • Streeten EA; Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
  • Albanes D; Population, Policy and Practice, University College London, Great Ormond Street, Institute of Child Health, London, WC1E 6BT, UK.
  • Lutsey PL; Kidney Research Institute, Division of Nephrology, 325 Ninth Avenue, Seattle, WA, 98104, USA.
  • Yao L; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Tang W; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Econs MJ; Department of Public Health & Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Wallaschofski H; Genetics and Personalized Medicine Program, University of Maryland School of Medicine, Howard Hall Room 567, Baltimore, MD, 21201, USA.
  • Völzke H; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
  • Zhou A; Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300S 2nd Street, Suite 300, Minneapolis, MN, 55454, USA.
  • Power C; Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300S 2nd Street, Suite 300, Minneapolis, MN, 55454, USA.
  • McCarthy MI; Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300S 2nd Street, Suite 300, Minneapolis, MN, 55454, USA.
  • Michos ED; Department of Medicine, Indiana University, Endocrinology, 1120W Michigan Street, Indianapolis, IN, 46202-5124, USA.
  • Boerwinkle E; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17489, Greifswald, Germany.
  • Weinstein SJ; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, 13316, Berlin, Germany.
  • Freedman ND; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, 13316, Berlin, Germany.
  • Huang WY; Institut für Community Medicine, SHIP/Klinisch-Epidemiologische Forschung, Universitätsmedizin Greifswald, Walther-Rathenau-Str. 48, 17475, Greifswald, Germany.
  • Van Schoor NM; Centre for Population Health Research, Sansom Institute for Health Research, University of South Australia, Adelaide, 5001, SA, Australia.
  • van der Velde N; Population, Policy and Practice, University College London, Great Ormond Street, Institute of Child Health, London, WC1E 6BT, UK.
  • Groot LCPGM; Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
  • Enneman A; Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK.
  • Cupples LA; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
  • Booth SL; Division of Cardiology, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
  • Vasan RS; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
  • Liu CT; Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Zhou Y; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
  • Ripatti S; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
  • Ohlsson C; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
  • Vandenput L; Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, De Boelelaan 1089a, 1081 HV, Amsterdam, The Netherlands.
  • Lorentzon M; Erasmus MC Department of Epidemiology, Postbus 2040, 3000CA, Rotterdam, The Netherlands.
  • Eriksson JG; AMC, Internal Medicine, Geriatrics Department, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
  • Shea MK; Department of Human Nutrition, Wageningen University, PO-box 17, 6700 AA, Wageningen, The Netherlands.
  • Houston DK; Erasmus MC Department of Epidemiology, Postbus 2040, 3000CA, Rotterdam, The Netherlands.
  • Kritchevsky SB; Department of Biostatistics, Boston University School of Public Health, Crosstown Center. 801 Massachusetts Avenue 3rd Floor, Boston, MA, 02118, USA.
  • Liu Y; Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.
  • Lohman KK; Vitamin K Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, USA.
  • Ferrucci L; Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.
Nat Commun ; 9(1): 260, 2018 01 17.
Article en En | MEDLINE | ID: mdl-29343764
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vitamina D / Proteínas de Transporte Vesicular / Población Blanca Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vitamina D / Proteínas de Transporte Vesicular / Población Blanca Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos