TY - JOUR
T1 - Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.
JF - Nat Commun
Y1 - 2017
A1 - Willems, Sara M
A1 - Wright, Daniel J
A1 - Day, Felix R
A1 - Trajanoska, Katerina
A1 - Joshi, Peter K
A1 - Morris, John A
A1 - Matteini, Amy M
A1 - Garton, Fleur C
A1 - Grarup, Niels
A1 - Oskolkov, Nikolay
A1 - Thalamuthu, Anbupalam
A1 - Mangino, Massimo
A1 - Liu, Jun
A1 - Demirkan, Ayse
A1 - Lek, Monkol
A1 - Xu, Liwen
A1 - Wang, Guan
A1 - Oldmeadow, Christopher
A1 - Gaulton, Kyle J
A1 - Lotta, Luca A
A1 - Miyamoto-Mikami, Eri
A1 - Rivas, Manuel A
A1 - White, Tom
A1 - Loh, Po-Ru
A1 - Aadahl, Mette
A1 - Amin, Najaf
A1 - Attia, John R
A1 - Austin, Krista
A1 - Benyamin, Beben
A1 - Brage, Søren
A1 - Cheng, Yu-Ching
A1 - Cięszczyk, Paweł
A1 - Derave, Wim
A1 - Eriksson, Karl-Fredrik
A1 - Eynon, Nir
A1 - Linneberg, Allan
A1 - Lucia, Alejandro
A1 - Massidda, Myosotis
A1 - Mitchell, Braxton D
A1 - Miyachi, Motohiko
A1 - Murakami, Haruka
A1 - Padmanabhan, Sandosh
A1 - Pandey, Ashutosh
A1 - Papadimitriou, Ioannis
A1 - Rajpal, Deepak K
A1 - Sale, Craig
A1 - Schnurr, Theresia M
A1 - Sessa, Francesco
A1 - Shrine, Nick
A1 - Tobin, Martin D
A1 - Varley, Ian
A1 - Wain, Louise V
A1 - Wray, Naomi R
A1 - Lindgren, Cecilia M
A1 - MacArthur, Daniel G
A1 - Waterworth, Dawn M
A1 - McCarthy, Mark I
A1 - Pedersen, Oluf
A1 - Khaw, Kay-Tee
A1 - Kiel, Douglas P
A1 - Pitsiladis, Yannis
A1 - Fuku, Noriyuki
A1 - Franks, Paul W
A1 - North, Kathryn N
A1 - van Duijn, Cornelia M
A1 - Mather, Karen A
A1 - Hansen, Torben
A1 - Hansson, Ola
A1 - Spector, Tim
A1 - Murabito, Joanne M
A1 - Richards, J Brent
A1 - Rivadeneira, Fernando
A1 - Langenberg, Claudia
A1 - Perry, John R B
A1 - Wareham, Nick J
A1 - Scott, Robert A
AB - 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) 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.

VL - 8
ER -