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Title: Large-Scale GWAS Identifies Multiple Loci for Hand Grip Strength Providing Biological Insights into Muscular Fitness
Authors: 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.
Miyamoto-Mikami, Eri
Luca A., Lotta
Rivas, Manuel A.
White, Tom
Loh, Po-Ru
Aadahl, Mette
Amin, Najaf
Attia, John R.
Austin, Krista
Benyamin, Beben
Brage, Søren
Cheng, Yu-Ching
Cięszczyk, Paweł
Derave, Wim
Eriksson, Karl-Fredrik
Eynon, Nir
Linneberg, Allan
Lucia, Alejandro
Massidda, Myosotis
Mitchell, Braxton D.
Miyachi, Motohiko
Murakami, Haruka
Padmanabhan, Sandosh
Pandey, Ashutosh
Papadimitriou, Ioannis
Rajpal, Deepak K.
Sale, Craig
Schnurr, Theresia M.
Sessa, Francesco
Shrine, Nick
Tobin, Martin D.
Varley, Ian
Wain, Louise V.
Wray, Naomi R.
Lindgren, Cecilia M.
MacArthur, Daniel G.
Waterworth, Dawn M.
McCarthy, Mark I.
Pedersen, Oluf
Khaw, Kay-Tee
Kiel, Douglas P.
Pitsiladis, Yannis
Fuku, Noriyuki
Franks, Paul W.
North, Kathryn N.
van Duijn, Cornelia M.
Mather, Karen A.
Hansen, Torben
Hansson, Ola
Spector, Tim
Murabito, Joanne M.
Richards, J. Brent
Rivadeneira, Fernando
Langenberg, Claudia
Perry, John R.B.
Wareham, Nick J.
Scott, Robert A.
First Published: 12-Jul-2017
Publisher: Nature Publishing Group
Citation: Nature Communications, 2017, 8:16015
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.
DOI Link: 10.1038/ncomms16015
ISSN: 2041-1723
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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