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Large-Scale GWAS Identifies Multiple Loci for Hand Grip Strength Providing Biological Insights into Muscular Fitness

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journal contribution
posted on 2017-07-11, 11:26 authored by Sara M. Willems, Daniel J. Wright, Felix R. Day, Katerina Trajanoska, Peter K. Joshi, John A. Morris, Amy M. Matteini, Fleur C. Garton, Niels Grarup, Nikolay Oskolkov, Anbupalam Thalamuthu, Massimo Mangino, Jun Liu, Ayse Demirkan, Monkol Lek, Liwen Xu, Guan Wang, Christopher Oldmeadow, Kyle J. Gaulton, Eri Miyamoto-Mikami, Lotta Luca A., Manuel A. Rivas, Tom White, Po-Ru Loh, Mette Aadahl, Najaf Amin, John R. Attia, Krista Austin, Beben Benyamin, Søren Brage, Yu-Ching Cheng, Paweł Cięszczyk, Wim Derave, Karl-Fredrik Eriksson, Nir Eynon, Allan Linneberg, Alejandro Lucia, Myosotis Massidda, Braxton D. Mitchell, Motohiko Miyachi, Haruka Murakami, Sandosh Padmanabhan, Ashutosh Pandey, Ioannis Papadimitriou, Deepak K. Rajpal, Craig Sale, Theresia M. Schnurr, Francesco Sessa, Nick Shrine, Martin D. Tobin, Ian Varley, Louise V. Wain, Naomi R. Wray, Cecilia M. Lindgren, Daniel G. MacArthur, Dawn M. Waterworth, Mark I. McCarthy, Oluf Pedersen, Kay-Tee Khaw, Douglas P. Kiel, Yannis Pitsiladis, Noriyuki Fuku, Paul W. Franks, Kathryn N. North, Cornelia M. van Duijn, Karen A. Mather, Torben Hansen, Ola Hansson, Tim Spector, Joanne M. Murabito, J. Brent Richards, Fernando Rivadeneira, Claudia Langenberg, John R.B. Perry, Nick J. Wareham, Robert A. Scott
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.



Nature Communications, 2017, 8:16015

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/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences


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