Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

GEFOS Anytype of Fracture Consortium

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Original languageEnglish (US)
Article number16015
JournalNature Communications
Volume8
DOIs
StatePublished - Jul 12 2017

Fingerprint

Signal transduction
fitness
Genome-Wide Association Study
Hand Strength
loci
Muscle
Genes
Fibers
mortality
muscular strength
Mendelian Randomization Analysis
muscle fibers
skeletal muscle
Psychomotor Disorders
Morbidity
impairment
Mortality
determinants
genes
markers

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. / GEFOS Anytype of Fracture Consortium.

In: Nature Communications, Vol. 8, 16015, 12.07.2017.

Research output: Contribution to journalArticle

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abstract = "Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.",
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