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

TitleGWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.
Publication TypeJournal Article
Year of Publication2016
AuthorsMatteini, AM, Tanaka, T, Karasik, D, Atzmon, G, Chou, W-C, Eicher, JD, Johnson, AD, Arnold, AM, Callisaya, ML, Davies, G, Evans, DS, Holtfreter, B, Lohman, K, Lunetta, KL, Mangino, M, Smith, AVernon, Smith, JA, Teumer, A, Yu, L, Arking, DE, Aron S. Buchman, Chibinik, LB, De Jager, PL, Faul, JD, Garcia, ME, Gillham-Nasenya, I, Gudnason, V, Hofman, A, Hsu, Y-H, Ittermann, T, Lahousse, L, Liewald, DC, Liu, Y, Lopez, L, Rivadeneira, F, Rotter, JI, Siggeirsdottir, K, Starr, JM, Thomson, R, Tranah, GJ, Uitterlinden, AG, Völker, U, Völzke, H, Weir, DR, Yaffe, K, Zhao, W, Zhuang, WV, Zmuda, JM, Bennett, DA, Cummings, SR, Deary, IJ, Ferrucci, L, Harris, TB, Kardia, SLR, Kocher, T, Kritchevsky, SB, Psaty, BM, Seshadri, S, Spector, TD, Srikanth, VK, B Windham, G, M Zillikens, C, Newman, AB, Walston, JD, Kiel, DP, Murabito, JM
JournalAging Cell
Volume15
Issue5
Pagination792-800
Date Published2016 Oct
ISSN Number1474-9726
KeywordsCHARGE, Genetics, Older Adults, Physical Ability
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.

DOI10.1111/acel.12468
Alternate JournalAging Cell
Citation Key8614
PubMed ID27325353
Grant ListRF1 AG015819 / AG / NIA NIH HHS / United States