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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
Jones, Garan; Trajanoska, Katerina; Santanasto, Adam J; Stringa, Najada; Kuo, Chia-Ling; Atkins, Janice L; Lewis, Joshua R; Duong, ThuyVy; Hong, Shengjun; Biggs, Mary L; Luan, Jian'an; Sarnowski, Chloe; Lunetta, Kathryn L; Tanaka, Toshiko; Wojczynski, Mary K; Cvejkus, Ryan; Nethander, Maria; Ghasemi, Sahar; Yang, Jingyun; Zillikens, M Carola; Walter, Stefan; Sicinski, Kamil; Kague, Erika; Ackert-Bicknell, Cheryl L; Arking, Dan E; Windham, B Gwen; Boerwinkle, Eric; Grove, Megan L; Graff, Misa; Spira, Dominik; Demuth, Ilja; van der Velde, Nathalie; de Groot, Lisette C P G M; Psaty, Bruce M; Odden, Michelle C; Fohner, Alison E; Langenberg, Claudia; Wareham, Nicholas J; Bandinelli, Stefania; van Schoor, Natasja M; Huisman, Martijn; Tan, Qihua; Zmuda, Joseph; Mellström, Dan; Karlsson, Magnus; Bennett, David A; Buchman, Aron S; De Jager, Philip L; Uitterlinden, Andre G; Völker, Uwe.
Afiliación
  • Jones G; Epidemiology and Public Health Group, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
  • Trajanoska K; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Santanasto AJ; Department of Epidemiology Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Stringa N; University of Pittsburgh, Department of Epidemiology, Pittsburgh, PA, USA.
  • Kuo CL; Department of Epidemiology and Biostatistics, Amsterdam UMC- Vrije Universiteit, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
  • Atkins JL; Biostatistics Center, Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT, USA.
  • Lewis JR; Epidemiology and Public Health Group, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
  • Duong T; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Hong S; School fo Public Health University of Sydney, Sydney, NSW, Australia.
  • Biggs ML; Medical School, University of Western Australia, Crawley, WA, Australia.
  • Luan J; McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sarnowski C; Lübeck Interdisciplinary Plattform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
  • Lunetta KL; Cardiovascular Health Research Unit, Department of Medicine, and Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Tanaka T; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
  • Wojczynski MK; Biostatistics Department, Boston University School of Public Health, Boston, MA, USA.
  • Cvejkus R; Biostatistics Department, Boston University School of Public Health, Boston, MA, USA.
  • Nethander M; Longitudinal Study Section, Translational Gerontology branch, National Institute on Aging, Baltimore, MD, USA.
  • Ghasemi S; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Yang J; University of Pittsburgh, Department of Epidemiology, Pittsburgh, PA, USA.
  • Zillikens MC; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Walter S; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Sicinski K; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  • Kague E; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Ackert-Bicknell CL; Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • Arking DE; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Windham BG; Department of Medicine and Public Health, Rey Juan Carlos University, Madrid, Spain.
  • Boerwinkle E; CIBER of Frailty and Healthy Aging (CIBERFES), Madrid, Spain.
  • Grove ML; Center for Demography of Health and Aging, University of Wisconsin-Madison, Madison, WI, USA.
  • Graff M; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
  • Spira D; Department of Orthopedics, University of Colorado, Aurora, CO, USA.
  • Demuth I; McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • van der Velde N; Department of Medicine/Geriatrics, University of Mississippi School of Medicine, Jackson, MS, USA.
  • de Groot LCPGM; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Psaty BM; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
  • Odden MC; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Fohner AE; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
  • Langenberg C; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Wareham NJ; Berlin Institute of Health, Department of Endocrinology and Metabolism, Berlin, Germany.
  • Bandinelli S; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • van Schoor NM; Berlin Institute of Health, Department of Endocrinology and Metabolism, Berlin, Germany.
  • Huisman M; Charité - Universitätsmedizin Berlin, BCRT - Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany.
  • Tan Q; Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
  • Zmuda J; Wageningen University, Division of Human Nutrition, PO-box 17, 6700 AA, Wageningen, The Netherlands.
  • Mellström D; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health services, University of Washington, Seattle, WA, USA.
  • Karlsson M; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
  • Bennett DA; Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
  • Buchman AS; Department of Epidemiology and Institute of Public Genetics, University of Washington, Seattle, WA, USA.
  • De Jager PL; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
  • Uitterlinden AG; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
  • Völker U; Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
Nat Commun ; 12(1): 654, 2021 01 28.
Article en En | MEDLINE | ID: mdl-33510174
ABSTRACT
Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Debilidad Muscular / Predisposición Genética a la Enfermedad / Estudio de Asociación del Genoma Completo / Sarcopenia Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Debilidad Muscular / Predisposición Genética a la Enfermedad / Estudio de Asociación del Genoma Completo / Sarcopenia Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido