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

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 ArkingAron S. Buchman, Lori B. Chibinik, Philip L. DeJager, 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)792-800
Number of pages9
JournalAging Cell
Volume15
Issue number5
DOIs
Publication statusPublished - Oct 1 2016

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Keywords

  • aging
  • genomewide association
  • meta-analysis
  • muscle strength
  • older adults
  • SNP

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Matteini, A. M., Tanaka, T., Karasik, D., Atzmon, G., Chou, W. C., Eicher, J. D., ... Murabito, J. M. (2016). GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell, 15(5), 792-800. https://doi.org/10.1111/acel.12468