Year: 2016
Type: article
Study design: Observational Study
Abstract: Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10(-8) ) and 39 suggestive (P-value< 5 × 10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.
Source: Aging Cell
DOI: 10.1111/acel.12468
Authors: Amy M. Matteini, Toshiko Tanaka, David Karasik, Gil Atzmon, Wen‐Chi Chou, John D. Eicher, Andrew D. Johnson, Alice M. Arnold, Michele L. Callisaya, Gail Davies, Daniel S. Evans, Birte Holtfreter, Kurt Lohman, Kathryn L. Lunetta, Massimo Mangino, Albert V. Smith, Jennifer A. Smith, Alexander Teumer, Lei Yu, Dan E. Arking, Aron S. Buchman, Lori B. Chibinik, Philip L. De Jager, Denis A. Evans, Jessica D. Faul, Melissa E. Garcia, Irina Gillham‐Nasenya, Vilmundur Gudnason, Albert Hofman, Yi‐Hsiang Hsu, Till Ittermann, Lies Lahousse, David C. Liewald, Yongmei Liu, Lorna Lopez, Fernando Rivadeneira, Jerome I. Rotter, Kristin Siggeirsdottir, John M. Starr, Russell Thomson, Gregory J. Tranah, André G. Uitterlinden, Uwe Völker, Henry Völzke, David R. Weir, Kristine Yaffe, Wei Zhao, Wei Vivian Zhuang, Joseph M. Zmuda, David A. Bennett, Steven R. Cummings, Ian J. Deary, Luigi Ferrucci, Tamara B. Harris, Sharon L. R. Kardia, Thomas Kocher, Stephen B. Kritchevsky, Bruce M. Psaty, Sudha Seshadri, Timothy D. Spector, Velandai K. Srikanth, B. Gwen Windham, M. Carola Zillikens, Anne B. Newman, Jeremy D. Walston, Douglas P. Kiel, Joanne M. Murabito
Institutions: Johns Hopkins University, Johns Hopkins Medicine, National Institute on Aging, Beth Israel Deaconess Medical Center, Bar-Ilan University, Hebrew SeniorLife, Albert Einstein College of Medicine, University of Haifa, National Heart, Lung, and Blood Institute, Framingham Heart Study, University of Washington, University of Tasmania, Menzies Institute for Medical Research, Monash University, University of Edinburgh, Rush University Medical Center, California Pacific Medical Center, Universitätsmedizin Greifswald, Universität Greifswald, Wake Forest University Health Sciences, Wake Forest University, Boston University, King's College London, Guy's and St Thomas' NHS Foundation Trust, Icelandic Heart Association, University of Michigan, Broad Institute, Brigham and Women's Hospital, Rush University, Institute for Social Research, National Institutes of Health, University of Iceland, Erasmus MC, Harvard University, Ghent University Hospital, Ghent University, Netherlands Consortium for Healthy Ageing, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Alzheimer Scotland, German Centre for Cardiovascular Research, German Center for Diabetes Research, San Francisco VA Medical Center, University of California, San Francisco, Creighton University, University of Pittsburgh, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, University of Mississippi Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: Eli Lilly and Company, Yale University, Johns Hopkins University, Wellcome Trust, Anatomical Society, Scottish Government, National Institute for Health and Care Research, Royal Society, Age UK, Bundesministerium für Bildung und Forschung, Fonds Wetenschappelijk Onderzoek, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Vlaamse regering, Hjartavernd, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
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OpenAlex ID: W2469110210