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

Nat Commun. 2017 Jul 12:8:16015. doi: 10.1038/ncomms16015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Genetic Loci
  • Genetics, Population*
  • Genome-Wide Association Study*
  • Hand / physiology*
  • Hand Strength*
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Repressor Proteins / genetics
  • Transforming Growth Factor alpha / genetics
  • United Kingdom
  • White People / genetics


  • ACTG1 protein, human
  • Actins
  • LRPPRC protein, human
  • Membrane Proteins
  • NSL1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • PEX14 protein, human
  • Repressor Proteins
  • TGFA protein, human
  • Transforming Growth Factor alpha