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

Tools

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. ORCID: 0000-0002-5816-4169, Schnurr, T.M., Sessa, F., Shrine, N., Tobin, M.D., Varley, I. ORCID: 0000-0002-3607-8921, 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., 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

Preview

Text
8789_Sale.pdf - Published version
Download (407kB) | Preview

Official URL: http://doi.org/10.1038/ncomms16015

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:

ISSN:

2041-1723

Identifiers: