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

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, 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 ORCID: 0000-0002-5816-4169, 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, Oei, L, Zheng, H-F, Forgetta, V, Leong, A, Ahmad, OS, Laurin, C, Mokry, LE, Ross, S, Elks, CE, Bowden, J, Warrington, NM, Murray, A, Ruth, KS, Tsilidis, KK, Medina-Gómez, C, Estrada, K, Bis, JC, Chasman, DI, Demissie, S, Enneman, AW, Hsu, Y-H, Ingvarsson, T, Kähönen, M, Kammerer, C, Lacroix, AZ, Li, G, Liu, C-T, Liu, Y, Lorentzon, M, Mägi, R, Mihailov, E, Milani, L, Moayyeri, A, Nielson, CM, Sham, PC, Siggeirsdotir, K, Sigurdsson, G, Stefansson, K, Trompet, S, Thorleifsson, G, Vandenput, L, van der Velde, N, Viikari, J, Xiao, S-M, Zhao, JH, Evans, DS, Cummings, SR, Cauley, J, Duncan, EL, de Groot, LCPGM, Esko, T, Gudnason, V, Harris, TB, Jackson, RD, Jukema, JW, Ikram, AMA, Karasik, D, Kaptoge, S, Kung, AWC, Lehtimäki, T, Lyytikäinen, L-P, Lips, P, Luben, R, Metspalu, A, van Meurs, JBJ, Minster, RL, Orwoll, E, Oei, E, Psaty, BM, Raitakari, OT, Ralston, SW, Ridker, PM, Robbins, JA, Smith, AV, Styrkarsdottir, U, Tranah, GJ, Thorstensdottir, U, Uitterlinden, AG, Zmuda, J, Zillikens, MC, Ntzani, EE, Evangelou, E, Ioannidis, JPA, Evans, DM, Ohlsson, C, 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 and Scott, RA, 2017. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications, 8, p. 16015. ISSN 2041-1723

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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.

Item Type: Journal article
Publication Title: Nature Communications
Creators: Willems, S.M., Wright, D.J., Day, F.R., Trajanoska, K., Joshi, P.K., Morris, J.A., Matteini, A.M., Garton, F.C., Grarup, N., Oskolkov, N., Thalamuthu, A., Mangino, M., Liu, J., Demirkan, A., Lek, M., Xu, L., Wang, G., Oldmeadow, C., Gaulton, K.J., Lotta, L.A., Miyamoto-Mikami, E., Rivas, M.A., White, T., Loh, P.R., Aadahl, M., Amin, N., Attia, J.R., 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, B.D., Miyachi, M., Murakami, H., Padmanabhan, S., Pandey, A., Papadimitriou, I., Rajpal, D.K., Sale, C., Schnurr, T.M., Sessa, F., Shrine, N., Tobin, M.D., Varley, I., Wain, L.V., Wray, N.R., Lindgren, C.M., MacArthur, D.G., Waterworth, D.M., McCarthy, M.I., Pedersen, O., Khaw, K.T., Kiel, D.P., Oei, L., Zheng, H.F., Forgetta, V., Leong, A., Ahmad, O.S., Laurin, C., Mokry, L.E., Ross, S., Elks, C.E., Bowden, J., Warrington, N.M., Murray, A., Ruth, K.S., Tsilidis, K.K., Medina-Gómez, C., Estrada, K., Bis, J.C., Chasman, D.I., Demissie, S., Enneman, A.W., Hsu, Y.H., Ingvarsson, T., Kähönen, M., Kammerer, C., Lacroix, A.Z., Li, G., Liu, C.T., Liu, Y., Lorentzon, M., Mägi, R., Mihailov, E., Milani, L., Moayyeri, A., Nielson, C.M., Sham, P.C., Siggeirsdotir, K., Sigurdsson, G., Stefansson, K., Trompet, S., Thorleifsson, G., Vandenput, L., van der Velde, N., Viikari, J., Xiao, S.M., Zhao, J.H., Evans, D.S., Cummings, S.R., Cauley, J., Duncan, E.L., de Groot, L.C.P.G.M., Esko, T., Gudnason, V., Harris, T.B., Jackson, R.D., Jukema, J.W., Ikram, A.M.A., Karasik, D., Kaptoge, S., Kung, A.W.C., Lehtimäki, T., Lyytikäinen, L.P., Lips, P., Luben, R., Metspalu, A., van Meurs, J.B.J., Minster, R.L., Orwoll, E., Oei, E., Psaty, B.M., Raitakari, O.T., Ralston, S.W., Ridker, P.M., Robbins, J.A., Smith, A.V., Styrkarsdottir, U., Tranah, G.J., Thorstensdottir, U., Uitterlinden, A.G., Zmuda, J., Zillikens, M.C., Ntzani, E.E., Evangelou, E., Ioannidis, J.P.A., Evans, D.M., Ohlsson, C., Pitsiladis, Y., Fuku, N., Franks, P.W., North, K.N., van Duijn, C.M., Mather, K.A., Hansen, T., Hansson, O., Spector, T., Murabito, J.M., Richards, J.B., Rivadeneira, F., Langenberg, C., Perry, J.R.B., Wareham, N.J. and Scott, R.A.
Publisher: Nature Publishing Group
Date: 12 July 2017
Volume: 8
ISSN: 2041-1723
Identifiers:
NumberType
10.1038/ncomms16015DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 13 Jul 2017 10:42
Last Modified: 13 Jul 2017 10:42
URI: http://irep.ntu.ac.uk/id/eprint/31227

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