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