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    GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium


    Matteini, Amy M., Tanaka, Toshiko, Karasik, David, Atzmon, Gil, Chou, Wen‐Chi, Eicher, John D., Johnson, Andrew D., Arnold, Alice M., Callisaya, Michele L., Davies, Gail, Evans, Daniel S., Holtfreter, Birte, Lohman, Kurt, Lunetta, Kathryn L., Mangino, Massimo, Smith, Albert V., Smith, Jennifer A., Teumer, Alexander, Yu, Lei, Arking, Dan E., Buchman, Aron S., Chibinik, Lori B., De Jager, Philip L., Evans, Denis A., Faul, Jessica D., Garcia, Melissa E., Gillham‐Nasenya, Irina, Gudnason, Vilmundur, Hofman, Albert, Hsu, Yi‐Hsiang, Ittermann, Till, Lahousse, Lies, Liewald, David C., Liu, Yongmei, Lopez, Lorna M., Rivadeneira, Fernando, Rotter, Jerome I., Siggeirsdottir, Kristin, Starr, John M., Thomson, Russell, Tranah, Gregory J., Uitterlinden, André G., Völker, Uwe, Völzke, Henry, Weir, David R., Yaffe, Kristine, Zhao, Wei, Zhuang, Wei Vivian, Zmuda, Joseph M., Bennett, David A., Cummings, Steven R., Deary, Ian J., Ferrucci, Luigi, Harris, Tamara B., Kardia, Sharon L. R., Kocher, Thomas, Kritchevsky, Stephen B., Psaty, Bruce M., Seshadri, Sudha, Spector, Timothy D., Srikanth, Velandai K., Windham, B. Gwen, Zillikens, M. Carola, Newman, Anne B., Walston, Jeremy D., Kiel, Douglas P. and Murabito, Joanne M. (2016) GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell, 15 (5). pp. 792-800. ISSN 1474-9718

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    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.
    Item Type: Article
    Keywords: aging; genomewide association; meta-analysis; muscle strength; older adults; SNP;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17199
    Identification Number: 10.1111/acel.12468
    Depositing User: Lorna Lopez
    Date Deposited: 17 May 2023 10:21
    Journal or Publication Title: Aging Cell
    Publisher: Wiley
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17199
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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