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

Sara M. Willems, Daniel J. Wright, Felix R. Day, Katerina Trajanoska, Peter K. Joshi, John A. Morris, Amy M. Matteini, Fleur C. Garton, Niels Grarup, Nikolay Oskolkov, Anbupalam Thalamuthu, Massimo Mangino, Jun Liu, Ayse Demirkan, Monkol Lek, Liwen Xu, Guan Wang, Christopher Oldmeadow, Kyle J. Gaulton, Luca A. LottaEri Miyamoto-Mikami, Manuel A. Rivas, Tom White, Po Ru Loh, Mette Aadahl, Najaf Amin, John R. Attia, Krista Austin, Beben Benyamin, Søren Brage, Yu Ching Cheng, Paweł Ciȩszczyk, Wim Derave, Karl Fredrik Eriksson, Nir Eynon, Allan Linneberg, Alejandro Lucia, Myosotis Massidda, Braxton D. Mitchell, Motohiko Miyachi, Haruka Murakami, Sandosh Padmanabhan, Ashutosh Pandey, Ioannis Papadimitriou, Deepak K. Rajpal, Craig Sale, Theresia M. Schnurr, Francesco Sessa, Nick Shrine, Martin D. Tobin, Ian Varley, Louise V. Wain, Naomi R. Wray, Cecilia M. Lindgren, Daniel G. MacArthur, Dawn M. Waterworth, Mark I. McCarthy, Oluf Pedersen, Kay Tee Khaw, Douglas P. Kiel, Yannis Pitsiladis, Noriyuki Fuku, Paul W. Franks, Kathryn N. North, Cornelia M. Van Duijn, Karen A. Mather, Torben Hansen, Ola Hansson, Tim Spector, Joanne M. Murabito, J. Brent Richards, Fernando Rivadeneira, Claudia Langenberg, John R.B. Perry, Nick J. Wareham*, Robert A. Scott, Ling Oei, Hou Feng Zheng, Vincenzo Forgetta, Aaron Leong, Omar S. Ahmad, Charles Laurin, Lauren E. Mokry, Stephanie Ross, Cathy E. Elks, Jack Bowden, Nicole M. Warrington, Anna Murray, Katherine S. Ruth, Konstantinos K. Tsilidis, Carolina Medina-Gómez, Karol Estrada, Joshua C. Bis, Daniel I. Chasman, Serkalem Demissie, Anke W. Enneman, Yi Hsiang Hsu, Thorvaldur Ingvarsson, Mika Kähönen, Candace Kammerer, Andrea Z. Lacroix, Guo Li, Ching Ti Liu, Yongmei Liu, Mattias Lorentzon, Reedik Mägi, Evelin Mihailov, Lili Milani, Alireza Moayyeri, Carrie M. Nielson, Pack Chung Sham, Kristin Siggeirsdotir, Gunnar Sigurdsson, Kari Stefansson, Stella Trompet, Gudmar Thorleifsson, Liesbeth Vandenput, Nathalie Van Der Velde, Jorma Viikari, Su Mei Xiao, Jing Hua Zhao, Daniel S. Evans, Steven R. Cummings, Jane Cauley, Emma L. Duncan, Lisette C.P.G.M. De Groot, Tonu Esko, Vilmundar Gudnason, Tamara B. Harris, Rebecca D. Jackson, J. Wouter Jukema, Arfan M.A. Ikram, David Karasik, Stephen Kaptoge, Annie Wai Chee Kung, Terho Lehtimäki, Leo Pekka Lyytikäinen, Paul Lips, Robert Luben, Andres Metspalu, Joyce B.J. Van Meurs, Ryan L. Minster, Erick Orwoll, Edwin Oei, Bruce M. Psaty, Olli T. Raitakari, Stuart W. Ralston, Paul M. Ridker, John A. Robbins, Albert V. Smith, Unnur Styrkarsdottir, Gregory J. Tranah, Unnur Thorstensdottir, Andre G. Uitterlinden, Joseph Zmuda, M. Carola Zillikens, Evangelia E. Ntzani, Evangelos Evangelou, John P.A. Ioannidis, David M. Evans, Claes Ohlsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number16015
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 12 Jul 2017

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