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

Willems, S. M. et al. (2017) Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications, 8, 16015. (doi: 10.1038/ncomms16015) (PMCID:PMC5510175)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Authors: 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., Lotta, L. A., Miyamoto-Mikami, E., Rivas, M. A., White, T., Loh, P.-R., Aadahl, M., Amin, N., Attia, J. R., Austin, K., Benyamin, B., Brage, S., Cheng, Y.-C., Cięszczyk, P., Derave, W., Eriksson, K.-F., Eynon, N., Linneberg, A., Lucia, A., Massidda, M., Mitchell, B. D., Miyachi, M., Murakami, H., Padmanabhan, S., Pandey, A., Papadimitriou, I., Rajpal, D. K., Sale, C., Schnurr, T. M., Sessa, F., Shrine, N., Tobin, M. D., Varley, I., Wain, L. V., Wray, N. R., Lindgren, C. M., MacArthur, D. G., Waterworth, D. M., McCarthy, M. I., Pedersen, O., Khaw, K.-T., Kiel, D. P., Oei, L., Zheng, H.-F., Forgetta, V., Leong, A., Ahmad, O. S., Laurin, C., Mokry, L. E., Ross, S., Elks, C. E., Bowden, J., Warrington, N. M., Murray, A., Ruth, K. S., Tsilidis, K. K., Medina-Gómez, C., Estrada, K., Bis, J. C., Chasman, D. I., Demissie, S., Enneman, A. W., Hsu, Y.-H., Ingvarsson, T., Kähönen, M., Kammerer, C., Lacroix, A. Z., Li, G., Liu, C.-T., Liu, Y., Lorentzon, M., Mägi, R., Mihailov, E., Milani, L., Moayyeri, A., Nielson, C. M., Sham, P. C., Siggeirsdotir, K., Sigurdsson, G., Stefansson, K., Trompet, S., Thorleifsson, G., Vandenput, L., van der Velde, N., Viikari, J., Xiao, S.-M., Zhao, J. H., Evans, D. S., Cummings, S. R., Cauley, J., Duncan, E. L., de Groot, L. C. P. G. M., Esko, T., Gudnason, V., Harris, T. B., Jackson, R. D., Jukema, J. W., Ikram, A. M. A., Karasik, D., Kaptoge, S., Kung, A. W. C., Lehtimäki, T., Lyytikäinen, L.-P., Lips, P., Luben, R., Metspalu, A., van Meurs, J. B. J., Minster, R. L., Orwoll, E., Oei, E., Psaty, B. M., Raitakari, O. T., Ralston, S. W., Ridker, P. M., Robbins, J. A., Smith, A. V., Styrkarsdottir, U., Tranah, G. J., Thorstensdottir, U., Uitterlinden, A. G., Zmuda, J., Zillikens, M. C., Ntzani, E. E., Evangelou, E., Ioannidis, J. P. A., Evans, D. M., Ohlsson, C., Pitsiladis, Y., Fuku, N., Franks, P. W., North, K. N., van Duijn, C. M., Mather, K. A., Hansen, T., Hansson, O., Spector, T., Murabito, J. M., Richards, J. B., Rivadeneira, F., Langenberg, C., Perry, J. R. B., Wareham, N. J., and Scott, R. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Nature Communications 8:16015
Publisher Policy:Reproduced under a Creative Commons License

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