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

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    Author
    Willems, SM; Wright, DJ; Day, FR; Trajanoska, K; Joshi, PK; Morris, JA; Matteini, AM; Garton, FC; Grarup, N; Oskolkov, N; ...
    Date
    2017-07-12
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Garton, Fleur; North, Kathryn
    Affiliation
    Paediatrics (RCH)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Willems, S. M., Wright, D. J., Day, F. R., Trajanoska, K., Joshi, P. K., Morris, J. A., Matteini, A. M., Garton, F. C., Grarup, N., Oskolkov, N., Thalamuthu, A., Mangino, M., Liu, J., Demirkan, A., Lek, M., Xu, L., Wang, G., Oldmeadow, C., Gaulton, K. J. ,... Scott, R. A. (2017). Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/ncomms16015.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254821
    DOI
    10.1038/ncomms16015
    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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