Dataset Information

Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.

ABSTRACT: We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength (P <5 × 10^-8). Of these, 64 were associated (P < 0.01 and consistent direction) also in the replication dataset (N = 111,610). eQTL analyses highlighted several genes known to play a role in neuro-developmental disorders or brain function, and the results from meta-analysis showed a significant enrichment of gene expression of brain-related transcripts. Further, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents' age of death and education. We also showed that grip strength had shared biological pathways with indicators of frailty, including cognitive performance scores. By use of Mendelian randomization, we provide evidence that higher grip strength is protective of both coronary heart disease (OR = 0.69, 95% CI 0.60-0.79, P < 0.0001) and atrial fibrillation (OR = 0.75, 95% CI 0.62-0.90, P = 0.003). In conclusion, our results show shared genetic aetiology between grip strength, and cardiometabolic and cognitive health; and suggest that maintaining muscular strength could prevent future cardiovascular events.

SUBMITTER: Tikkanen E

PROVIDER: S-EPMC5915424 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.

Tikkanen Emmi E Gustafsson Stefan S Amar David D Shcherbina Anna A Waggott Daryl D Ashley Euan A EA Ingelsson Erik E

Scientific reports 20180424 1

We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength (P <5 × 10<sup>-8</sup>). Of these, 64 were associated (P < 0.01 and consistent direction) also in the replication dataset (N = 111,610). eQTL analyses highlighted s ...[more]

PMID: 29691431

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Project description:BackgroundDepression and anxiety are the leading mental health problems worldwide; depression is ranked as the leading cause of global disability with anxiety disorders ranked sixth. Preventive strategies based on the identification of modifiable factors merit exploration. The aim of the present study was to investigate the associations of handgrip strength (HGS) with incident depression and anxiety and to explore how these associations differ by socio-demographic, lifestyle, and health-related factors.MethodsThe analytic sample comprised 162 167 participants (55% women), aged 38-70 years, from the UK Biobank prospective cohort study. HGS was assessed at baseline using dynamometry. Depression and anxiety were extracted from primary care and hospital admission records. Cox proportional models were applied, with a 2 year landmark analysis, to investigate the associations between HGS and incident depression and anxiety.ResultsOf the 162 167 participants included, 5462 (3.4%) developed depression and 6614 (4.1%) anxiety, over a median follow-up period of 10.0 years (inter-quartile range: 9.3-10.8) for depression and 9.9 (inter-quartile range: 9.0-10.8) for anxiety. In the fully adjusted model, a 5 kg lower HGS was associated with a 7% (HR: 1.07 [95% CI: 1.05, 1.10]; P < 0.001) and 8% (HR: 1.08 [95% CI: 1.06, 1.10]; P < 0.001) higher risk of depression and anxiety, respectively. Compared with participants in the sex and age-specific highest tertiles of HGS, those in the medium and lowest tertiles had an 11% (HR: 1.11 [95% CI: 1.04, 1.19]; P = 0.002) and 24% (HR: 1.24 [95% CI: 1.16, 1.33]; P < 0.001) higher risk of depression and 13% (HR: 1.13 [95% CI: 1.06, 1.20]; P < 0.001) and 27% (HR: 1.27 [95% CI: 1.19, 1.35]; P < 0.001) higher risk of anxiety, respectively. The association of HGS with depression was stronger among participants with average or brisk walking pace (vs. slow walking pace; Pinteraction < 0.001). The association with anxiety was stronger in those participants aged ≥58 years (vs. ≤58 years; Pinteraction = 0.002) and those living in more affluent areas (vs. deprived; Pinteraction = 0.001).ConclusionsHandgrip strength was inversely associated with incident depression and anxiety. Because HGS is a simple, non-invasive, and inexpensive measure, it could be easily used in clinical practice to stratify patients and identify those at elevated risk of mental health problems. However, future research should assess if resistance training aimed at increasing HGS can prevent the occurrence of mental health conditions.

Project description:BackgroundMuscle weakness, which increases in prevalence with age, is a major public health concern. Grip strength is commonly used to identify weakness and an improved understanding of its determinants is required. We aimed to investigate if total and central adiposity are causally associated with grip strength.MethodsUp to 470,786 UK Biobank participants, aged 38-73 years, with baseline data on four adiposity indicators (body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-hip-ratio (WHR)) and maximum grip strength were included. We examined sex-specific associations between each adiposity indicator and grip strength. We explored whether associations varied by age, by examining age-stratified associations (< 50 years, 50-59 years, 60-64 years,65 years +). Using Mendelian randomisation (MR), we estimated the strength of the adiposity-grip strength associations using genetic instruments for each adiposity trait as our exposure.ResultsIn males, observed and MR associations were generally consistent: higher BMI and WC were associated with stronger grip; higher BF% and WHR were associated with weaker grip: 1-SD higher BMI was associated with 0.49 kg (95% CI: 0.45 kg, 0.53 kg) stronger grip; 1-SD higher WHR was associated with 0.45 kg (95% CI:0.41 kg, 0.48 kg) weaker grip (covariate adjusted observational analyses). Associations of BMI and WC with grip strength were weaker at older ages: in males aged < 50 years and 65 years + , 1-SD higher BMI was associated with 0.93 kg (95% CI: 0.84 kg, 1.01 kg) and 0.13 kg (95% CI: 0.05 kg, 0.21 kg) stronger grip, respectively. In females, higher BF% was associated with weaker grip and higher WC was associated with stronger grip; other associations were inconsistent.ConclusionsUsing different methods to triangulate evidence, our findings suggest causal links between adiposity and grip strength. Specifically, higher BF% (in both sexes) and WHR (males only) were associated with weaker grip strength.

Dataset Information

Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.

Publications

Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.

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