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

Journal article

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, Oskolkov, Nikolay, Thalamuthu, Anbupalam, Mangino, Massimo, Liu, Jun, Demirkan, Ayse, Lek, Monkol, Xu, Liwen, Wang, Guan, Oldmeadow, Christopher, Gaulton, Kyle J., ... Benyamin, Beben. (2017). Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications. 8(1), pp. 1 - 12. https://doi.org/10.1038/ncomms16015
AuthorsWillems, Sara M., Wright, Daniel J., Day, Felix R., Trajanoska, Katerina, Joshi, Peter K., Morris, John A., Matteini, Amy M., Garton, Fleur C., Grarup, Niels, Oskolkov, Nikolay, Thalamuthu, Anbupalam, Mangino, Massimo, Liu, Jun, Demirkan, Ayse, Lek, Monkol, Xu, Liwen, Wang, Guan, Oldmeadow, Christopher, Gaulton, Kyle J., Lotta, Luca A., Miyamoto-Mikami, Eri, Rivas, Manuel A., White, Tom, Loh, Po-Ru, Aadahl, Mette, Amin, Najaf, Attia, John R., Austin, Krista and Benyamin, Beben
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.

Year2017
JournalNature Communications
Journal citation8 (1), pp. 1 - 12
PublisherNature Publishing Group
ISSN2041-1723
Digital Object Identifier (DOI)https://doi.org/10.1038/ncomms16015
Scopus EID2-s2.0-85024482942
Open accessOpen access
Page range1 - 12
Research GroupMary MacKillop Institute for Health Research
Publisher's version
License
Grant IDNHMRC/568969
NHMRC/350833
Additional information

Please refer to the full article for a complete list of author names.

Place of publicationUnited Kingdom
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