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

Publication ,  Journal Article
Matteini, AM; Tanaka, T; Karasik, D; Atzmon, G; Chou, W-C; Eicher, JD; Johnson, AD; Arnold, AM; Callisaya, ML; Davies, G; Evans, DS; Lohman, K ...
Published in: Aging Cell
October 2016

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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Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

October 2016

Volume

15

Issue

5

Start / End Page

792 / 800

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Muscle Strength
  • Molecular Sequence Annotation
  • Humans
  • Hand Strength
  • Genome-Wide Association Study
  • Epigenesis, Genetic
  • Developmental Biology
 

Citation

APA
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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
Matteini, Amy M., Toshiko Tanaka, David Karasik, Gil Atzmon, Wen-Chi Chou, John D. Eicher, Andrew D. Johnson, et al. “GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.Aging Cell 15, no. 5 (October 2016): 792–800. https://doi.org/10.1111/acel.12468.
Matteini AM, Tanaka T, Karasik D, Atzmon G, Chou W-C, Eicher JD, et al. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell. 2016 Oct;15(5):792–800.
Matteini, Amy M., et al. “GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.Aging Cell, vol. 15, no. 5, Oct. 2016, pp. 792–800. Pubmed, doi:10.1111/acel.12468.
Matteini 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 AV, Smith JA, Teumer A, Yu L, Arking DE, Buchman AS, Chibinik LB, De Jager PL, Evans DA, 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, Windham BG, Zillikens MC, Newman AB, Walston JD, Kiel DP, Murabito JM. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell. 2016 Oct;15(5):792–800.
Journal cover image

Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

October 2016

Volume

15

Issue

5

Start / End Page

792 / 800

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Muscle Strength
  • Molecular Sequence Annotation
  • Humans
  • Hand Strength
  • Genome-Wide Association Study
  • Epigenesis, Genetic
  • Developmental Biology