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

TitleLarge-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.
Publication TypeJournal Article
Year of Publication2017
AuthorsWillems, 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, Cięszczyk, 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, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, J Richards, B, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA
Corporate/Institutional AuthorsGEFOS Any-Type of Fracture Consortium
JournalNat Commun
Date Published2017 Jul 12
Abstract<p>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.</p>
Alternate JournalNat Commun
PubMed ID29313844
PubMed Central IDPMC5510175
Grant ListUL1 TR002369 / TR / NCATS NIH HHS / United States
R01 AR041398 / AR / NIAMS NIH HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
MC_UU_12015/2 / / Medical Research Council / United Kingdom
P30 DK072488 / DK / NIDDK NIH HHS / United States
U24 AG051129 / AG / NIA NIH HHS / United States
U01 HG004436 / HG / NHGRI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
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