Dataset Information

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

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 (? = 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-? (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.

SUBMITTER: Matteini AM

PROVIDER: S-EPMC5013019 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Matteini Amy M AM Tanaka Toshiko T Karasik David D Atzmon Gil G Chou Wen-Chi WC Eicher John D JD Johnson Andrew D AD Arnold Alice M AM Callisaya Michele L ML Davies Gail G Evans Daniel S DS Holtfreter Birte B Lohman Kurt K Lunetta Kathryn L KL Mangino Massimo M Smith Albert V AV Smith Jennifer A JA Teumer Alexander A Yu Lei L Arking Dan E DE Buchman Aron S AS Chibinik Lori B LB De Jager Philip L PL Evans Denis A DA Faul Jessica D JD Garcia Melissa E ME Gillham-Nasenya Irina I Gudnason Vilmundur V Hofman Albert A Hsu Yi-Hsiang YH Ittermann Till T Lahousse Lies L Liewald David C DC Liu Yongmei Y Lopez Lorna L Rivadeneira Fernando F Rotter Jerome I JI Siggeirsdottir Kristin K Starr John M JM Thomson Russell R Tranah Gregory J GJ Uitterlinden André G AG Völker Uwe U Völzke Henry H Weir David R DR Yaffe Kristine K Zhao Wei W Zhuang Wei Vivian WV Zmuda Joseph M JM Bennett David A DA Cummings Steven R SR Deary Ian J IJ Ferrucci Luigi L Harris Tamara B TB Kardia Sharon L R SL Kocher Thomas T Kritchevsky Stephen B SB Psaty Bruce M BM Seshadri Sudha S Spector Timothy D TD Srikanth Velandai K VK Windham B Gwen BG Zillikens M Carola MC Newman Anne B AB Walston Jeremy D JD Kiel Douglas P DP Murabito Joanne M JM

Aging cell 20160621 5

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 analy ...[more]

PMID: 27325353

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Project description:ObjectiveThe purposes of this study were three-fold: (i) to describe handgrip strength in older individuals aged ≥60 years in Colombia; (ii) to identify sex-specific and age-specific muscle weakness cut-off points in older adults; and (iii) to determine the odds of adverse events for each of the intrinsic capacity domains for individuals with handgrip strength greater than the muscle weakness cut-off points, as compared with their weaker counterparts.MethodsA cross-sectional study was conducted in Colombia, among 5237 older adults aged ≥60 years old (58.5% women, 70.5 ± 7.8 years), according to 'SABE Survey 2015'. Handgrip strength data were obtained with a Takei dynamometer. Sociodemographic variables, five domains of intrinsic capacity (i.e. locomotion, vitality, cognition, psychological, and sensory), and medical conditions were assessed and analyzed. Adjustments variables were age, ethnicity, socio-economic status, urbanicity, body mass index, smoking status, alcohol intake, drug use, physical activity, and co-morbid chronic diseases. Sex-stratified analyses were conducted with logistic regression models.ResultsHandgrip strength was greater among men than among women (26.7 ± 8.5 vs. 16.7 ± 5.7 kg, respectively, P < 0.001) at all ages. Weak handgrip strength cut-off points ranged from 17.4 to 8.6 and from 10.1 to 4.9 in men and women, respectively. Overall, participants with optimal handgrip strength had better intrinsic capacity [in men, odds ratio (OR) = 0.62, 95% confidence interval (CI) 0.53 to 0.71; P < 0.001; and in women, OR = 0.79, 95% CI 0.68 to 0.92; P = 0.002] than their weaker counterparts. Also, men with optimal handgrip strength had a lower risk of hospitalization (OR = 0.47, 95% CI 0.29 to 0.78; P = 0.004) than their weaker counterparts.ConclusionsThis study is the first to describe handgrip strength values and cut-off points for muscle weakness among a nationally representative sample of Colombian older adults by age and sex. After categorizing older adults as weak or not weak based on the handgrip cut-off points, non-weakness was associated with a decreased odds of intrinsic capacity impairments. These cut-off points may be good candidates for clinical assessment of risks to physical and mental health in older Colombian adults.

Dataset Information

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

Publications

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

Similar Datasets

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