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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Willems, SM; Wright, DJ; Day, FR; Trajanoska, K; Joshi, PK; Morris, JA; Matteini, AM; Garton, FC; Grarup, N; Oskolkov, N; Thalamuthu, A; Mangino, M; Liu, J; Demirkan, A; Lek, M; Xu, L; Wang, G; Oldmeadow, C; Gaulton, KJ; Lotta, LA; Miyamoto-Mikami, E; Rivas, MA; White, T; Loh, P-R; Aadahl, M; Amin, N; Attia, JR; Austin, K; Benyamin, B; Brage, S; Cheng, Y-C; Cińôszczyk, P; Derave, W; Eriksson, K-F; Eynon, N; Linneberg, A; Lucia, A; Massidda, M; Mitchell, BD; Miyachi, M; Murakami, H; Padmanabhan, S; Pandey, A; Papadimitriou, I; Rajpal, DK; Sale, C; Schnurr, TM; Sessa, F; Shrine, N; Tobin, MD; Varley, I; Wain, LV; Wray, NR; Lindgren, CM; MacArthur, DG; Waterworth, DM; McCarthy, MI; Pedersen, O; Khaw, K-T; Kiel, DP; GEFOS Any-Type of Fracture Consortium, ; Pitsiladis, Y; Fuku, N; Franks, PW; North, KN; van Duijn, CM; Mather, KA; Hansen, T; Hansson, O; Spector, T; Murabito, JM; Richards, JB; Rivadeneira, F; Langenberg, C; Perry, JRB; Wareham, NJ; Scott, RA

Published Date

  • July 12, 2017

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 16015 -

PubMed ID

  • 29313844

Pubmed Central ID

  • PMC5510175

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms16015


  • eng

Conference Location

  • England