TY - JOUR
T1 - Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
AU - GEFOS Anytype of Fracture Consortium
AU - Willems, Sara M.
AU - Wright, Daniel J.
AU - Day, Felix R.
AU - Trajanoska, Katerina
AU - Joshi, Peter K.
AU - Morris, John A.
AU - Matteini, Amy M.
AU - Garton, Fleur C.
AU - Grarup, Niels
AU - Oskolkov, Nikolay
AU - Thalamuthu, Anbupalam
AU - Mangino, Massimo
AU - Liu, Jun
AU - Demirkan, Ayse
AU - Lek, Monkol
AU - Xu, Liwen
AU - Wang, Guan
AU - Oldmeadow, Christopher
AU - Gaulton, Kyle J.
AU - Lotta, Luca A.
AU - Miyamoto-Mikami, Eri
AU - Rivas, Manuel A.
AU - White, Tom
AU - Loh, Po Ru
AU - Aadahl, Mette
AU - Amin, Najaf
AU - Attia, John R.
AU - Austin, Krista
AU - Benyamin, Beben
AU - Brage, Søren
AU - Cheng, Yu Ching
AU - Ciȩszczyk, Paweł
AU - Derave, Wim
AU - Eriksson, Karl Fredrik
AU - Eynon, Nir
AU - Linneberg, Allan
AU - Lucia, Alejandro
AU - Massidda, Myosotis
AU - Mitchell, Braxton D.
AU - Miyachi, Motohiko
AU - Murakami, Haruka
AU - Padmanabhan, Sandosh
AU - Pandey, Ashutosh
AU - Papadimitriou, Ioannis
AU - Rajpal, Deepak K.
AU - Sale, Craig
AU - Schnurr, Theresia M.
AU - Sessa, Francesco
AU - Nielson, Carrie M.
AU - Orwoll, Erick
N1 - Publisher Copyright:
© The Author(s) 2017.
PY - 2017/7/12
Y1 - 2017/7/12
N2 - 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.
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 × 10-8) 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.
UR - http://www.scopus.com/inward/record.url?scp=85024482942&partnerID=8YFLogxK
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U2 - 10.1038/ncomms16015
DO - 10.1038/ncomms16015
M3 - Article
C2 - 29313844
AN - SCOPUS:85024482942
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
M1 - 16015
ER -