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

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Matteini, AM and Tanaka, T and Karasik, D and Atzmon, G and Chou, W-C and Eicher, JD and Johnson, AD and Arnold, AM and Callisaya, ML and Davies, G and Evans, DS and Holtfreter, B and Lohman, K and Lunetta, KL and Mangino, M and Smith, AV and Smith, JA and Teumer, A and Yu, L and Arking, DE and Buchman, AS and Chibinik, LB and De Jager, PL and Evans, DA and Faul, JD and Garcia, ME and Gillham-Nasenya, I and Gudnason, V and Hofman, A and Hsu, Y-H and Ittermann, T and Lahousse, L and Liewald, DC and Liu, Y and Lopez, L and Rivadeneira, F and Rotter, JI and Siggeirsdottir, K and Starr, JM and Thomson, R and Tranah, GJ and Uitterlinden, AG and Volker, U and Volzke, H and Weir, DR and Yaffe, K and Zhao, W and Zhuang, WV and Zmuda, JM and Bennett, DA and Cummings, SR and Deary, IJ and Ferrucci, L and Harris, TB and Kardia, SLR and Kocher, T and Kritchevsky, SB and Psaty, BM and Seshadri, S and Spector, TD and Srikanth, VK and Windham, BG and Zillikens, MC and Newman, AB and Walston, JD and Kiel, DP and Murabito, JM, 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 (2016) [Refereed Article]


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Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1111/acel.12468

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 Details

Item Type:Refereed Article
Keywords:SNP, aging, genomewide association, meta-analysis, muscle strength, older adults
Research Division:Medical and Health Sciences
Research Group:Public Health and Health Services
Research Field:Aged Health Care
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skeletal System and Disorders (incl. Arthritis)
Author:Callisaya, ML (Dr Michele Callisaya)
Author:Thomson, R (Dr Russell Thomson)
Author:Srikanth, VK (Dr Velandai Srikanth)
ID Code:109757
Year Published:2016
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-06-29
Last Modified:2017-02-22
Downloads:47 View Download Statistics

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