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Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.
Alonso, Nerea; Estrada, Karol; Albagha, Omar M E; Herrera, Lizbeth; Reppe, Sjur; Olstad, Ole K; Gautvik, Kaare M; Ryan, Niamh M; Evans, Kathryn L; Nielson, Carrie M; Hsu, Yi-Hsiang; Kiel, Douglas P; Markozannes, George; Ntzani, Evangelia E; Evangelou, Evangelos; Feenstra, Bjarke; Liu, Xueping; Melbye, Mads; Masi, Laura; Brandi, Maria Luisa; Riches, Philip; Daroszewska, Anna; Olmos, José Manuel; Valero, Carmen; Castillo, Jesús; Riancho, José A; Husted, Lise B; Langdahl, Bente L; Brown, Matthew A; Duncan, Emma L; Kaptoge, Stephen; Khaw, Kay-Tee; Usategui-Martín, Ricardo; Del Pino-Montes, Javier; González-Sarmiento, Rogelio; Lewis, Joshua R; Prince, Richard L; D'Amelio, Patrizia; García-Giralt, Natalia; Nogués, Xavier; Mencej-Bedrac, Simona; Marc, Janja; Wolstein, Orit; Eisman, John A; Oei, Ling; Medina-Gómez, Carolina; Schraut, Katharina E; Navarro, Pau; Wilson, James F; Davies, Gail.
  • Alonso N; Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Estrada K; Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
  • Albagha OME; Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Herrera L; Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
  • Reppe S; Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
  • Olstad OK; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
  • Gautvik KM; Department of Clinical Biochemistry, Lovisenberg Diakonale Hospital, Oslo, Norway.
  • Ryan NM; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  • Evans KL; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
  • Nielson CM; Department of Clinical Biochemistry, Lovisenberg Diakonale Hospital, Oslo, Norway.
  • Hsu YH; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  • Kiel DP; Centre for Genomic and Experimental Medicine, IGMM, University of Edinburgh, Edinburgh, UK.
  • Markozannes G; Centre for Genomic and Experimental Medicine, IGMM, University of Edinburgh, Edinburgh, UK.
  • Ntzani EE; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Evangelou E; Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon, USA.
  • Feenstra B; Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Liu X; BROAD Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Melbye M; Musculoskeletal Research Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.
  • Masi L; BROAD Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Brandi ML; Musculoskeletal Research Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.
  • Riches P; Harvard Medical School, Boston, Massachusetts, USA.
  • Daroszewska A; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Olmos JM; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Valero C; Centre for Evidence Synthesis in Health, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Rhode Island, USA.
  • Castillo J; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Riancho JA; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Husted LB; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Langdahl BL; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Brown MA; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Duncan EL; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Kaptoge S; Department of Medicine, Stanford School of Medicine, Stanford, California, USA.
  • Khaw KT; Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
  • Usategui-Martín R; Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
  • Del Pino-Montes J; Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • González-Sarmiento R; Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Lewis JR; Institute of Ageing and Chronic Disease, The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, Liverpool, UK.
  • Prince RL; Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, IDIVAL, RETICEF, Santander, Spain.
  • D'Amelio P; Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, IDIVAL, RETICEF, Santander, Spain.
  • García-Giralt N; Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, IDIVAL, RETICEF, Santander, Spain.
  • Nogués X; Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, IDIVAL, RETICEF, Santander, Spain.
  • Mencej-Bedrac S; Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, Aarhus, Denmark.
  • Marc J; Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, Aarhus, Denmark.
  • Wolstein O; Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Eisman JA; Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Oei L; Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
  • Medina-Gómez C; Department of Endocrinology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
  • Schraut KE; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Navarro P; Department of Public Health and Primary Care, School of Medicine, University of Cambridge, Cambridge, UK.
  • Wilson JF; Molecular Medicine Unit, Department of Medicine and Biomedical Research Institute of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca - CSIC, Salamanca, Spain.
  • Davies G; Molecular Medicine Unit, Department of Medicine and Biomedical Research Institute of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca - CSIC, Salamanca, Spain.
Ann Rheum Dis ; 77(3): 378-385, 2018 03.
Article en En | MEDLINE | ID: mdl-29170203
ABSTRACT

OBJECTIVES:

To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis.

METHODS:

Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies.

RESULTS:

A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures.

CONCLUSION:

We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cromosomas Humanos Par 2 / Fracturas de la Columna Vertebral / Fracturas Osteoporóticas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Middle aged Idioma: En Año: 2018 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cromosomas Humanos Par 2 / Fracturas de la Columna Vertebral / Fracturas Osteoporóticas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Middle aged Idioma: En Año: 2018 Tipo del documento: Article