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

Willems, Sara M; Wright, Daniel J.; Day, Felix R; Trajanoska, Katerina; Joshi, Peter K.; Morris, John A.; Matteini, Amy M.; Garton, Fleur C.; Grarup, Niels and Oskolkov, Nikolay LU , et al. (2017) In Nature Communications 8.
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... (More)

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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Nature Communications
volume
8
publisher
Nature Publishing Group
external identifiers
  • scopus:85024482942
  • wos:000405270700002
ISSN
2041-1723
DOI
10.1038/ncomms16015
language
English
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yes
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d51024e0-6b80-4e15-a890-7e4e996f6d3f
date added to LUP
2017-07-31 10:51:31
date last changed
2019-11-13 04:45:32
@article{d51024e0-6b80-4e15-a890-7e4e996f6d3f,
  abstract     = {<p>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&lt;5 × 10<sup>-8</sup>) 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.</p>},
  articleno    = {16015},
  author       = {Willems, Sara M and Wright, Daniel J. and Day, Felix R and Trajanoska, Katerina and Joshi, Peter K. and Morris, John A. and Matteini, Amy M. and Garton, Fleur C. and Grarup, Niels and Oskolkov, Nikolay and Thalamuthu, Anbupalam and Mangino, Massimo and Liu, Jun and Demirkan, Ayse and Lek, Monkol and Xu, Liwen and Wang, Guan and Oldmeadow, Christopher and Gaulton, Kyle J and Lotta, Luca A. and Miyamoto-Mikami, Eri and Rivas, Manuel A. and White, Tom and Loh, Po Ru and Aadahl, Mette and Amin, Najaf and Attia, John R and Austin, Krista and Benyamin, Beben and Brage, Søren and Cheng, Yu Ching and Ciȩszczyk, Paweł and Derave, Wim and Eriksson, Karl Fredrik and Eynon, Nir and Linneberg, Allan and Lucia, Alejandro and Massidda, Myosotis and Mitchell, Braxton D. and Miyachi, Motohiko and Murakami, Haruka and Padmanabhan, Sandosh and Pandey, Ashutosh and Papadimitriou, Ioannis and Rajpal, Deepak K. and Sale, Craig and Lindgren, Cecilia M. and Franks, Paul W. and Hansson, Ola and Ingvarsson, Thorvaldur and , },
  issn         = {2041-1723},
  language     = {eng},
  month        = {07},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness},
  url          = {http://dx.doi.org/10.1038/ncomms16015},
  volume       = {8},
  year         = {2017},
}