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

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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 x 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.
Keywords
Exercise Physiology and nutrition, GENOME-WIDE ASSOCIATION, GROWTH-FACTOR-ALPHA, MENDELIAN RANDOMIZATION, SKELETAL-MUSCLE, GENETIC INFLUENCES, METAANALYSIS, DISEASE, INSTRUMENTS, FRACTURES, VARIANTS

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Chicago
Willems, Sara M, Daniel J Wright, Felix R Day, Katerina Trajanoska, Peter K Joshi, John A Morris, Amy M Matteini, et al. 2017. “Large-scale GWAS Identifies Multiple Loci for Hand Grip Strength Providing Biological Insights into Muscular Fitness.” Nature Communications 8.
APA
Willems, S. M., Wright, D. J., Day, F. R., Trajanoska, K., Joshi, P. K., Morris, J. A., Matteini, A. M., et al. (2017). Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. NATURE COMMUNICATIONS, 8.
Vancouver
1.
Willems SM, Wright DJ, Day FR, Trajanoska K, Joshi PK, Morris JA, et al. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. NATURE COMMUNICATIONS. 2017;8.
MLA
Willems, Sara M, Daniel J Wright, Felix R Day, et al. “Large-scale GWAS Identifies Multiple Loci for Hand Grip Strength Providing Biological Insights into Muscular Fitness.” NATURE COMMUNICATIONS 8 (2017): n. pag. Print.
@article{8531104,
  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{\textlangle}5 x 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.},
  articleno    = {16015},
  author       = {Willems, Sara M and Wright, Daniel J and Day, Felix R and Trajanoska, Katerina and Joshi, Peter K and Morris, John A and Matteini, Amy M and Garton, Fleur C and Grarup, Niels and Oskolkov, Nikolay and Thalamuthu, Anbupalam and Mangino, Massimo and Liu, Jun and Demirkan, Ayse and Lek, Monkol and Xu, Liwen and Wang, Guan and Oldmeadow, Christopher and Gaulton, Kyle J and Lotta, Luca A and Miyamoto-Mikami, Eri and Rivas, Manuel A and White, Tom and Loh, Po-Ru and Aadahl, Mette and Amin, Najaf and Attia, John R and Austin, Krista and Benyamin, Beben and Brage, S{\o}ren and Cheng, Yu-Ching and Ci\k{e}szczyk, Pawe\unmatched{0142} and Derave, Wim and Eriksson, Karl-Fredrik and Eynon, Nir and Linneberg, Allan and Lucia, Alejandro and Massidda, Myosotis and Mitchell, Braxton D and Miyachi, Motohiko and Murakami, Haruka and Padmanabhan, Sandosh and Pandey, Ashutosh and Papadimitriou, Ioannis and Rajpal, Deepak K and Sale, Craig and Schnurr, Theresia M and Sessa, Francesco and Shrine, Nick and Tobin, Martin D and Varley, Ian and Wain, Louise V and Wray, Naomi R and Lindgren, Cecilia M and MacArthur, Daniel G and Waterworth, Dawn M and McCarthy, Mark I and Pedersen, Oluf and Khaw, Kay-Tee and Kiel, Douglas P and Oei, Ling and Zheng, Hou-Feng and Forgetta, Vincenzo and Leong, Aaron and Ahmad, Omar S and Laurin, Charles and Mokry, Lauren E and Ross, Stephanie and Elks, Cathy E and Bowden, Jack and Warrington, Nicole M and Murray, Anna and Ruth, Katherine S and Tsilidis, Konstantinos K and Medina-G{\'o}mez, Carolina and Estrada, Karol and Bis, Joshua C and Chasman, Daniel I and Demissie, Serkalem and Enneman, Anke W and Hsu, Yi-Hsiang and Ingvarsson, Thorvaldur and K{\"a}h{\"o}nen, Mika and Kammerer, Candace and Lacroix, Andrea Z and Li, Guo and Liu, Ching-Ti and Liu, Yongmei and Lorentzon, Mattias and M{\"a}gi, Reedik and Mihailov, Evelin and Milani, Lili and Moayyeri, Alireza and Nielson, Carrie M and Sham, Pack Chung and Siggeirsdotir, Kristin and Sigurdsson, Gunnar and Stefansson, Kari and Trompet, Stella and Thorleifsson, Gudmar and Vandenput, Liesbeth and van der Velde, Nathalie and Viikari, Jorma and Xiao, Su-Mei and Zhao, Jing Hua and Evans, Daniel S and Cummings, Steven R and Cauley, Jane and Duncan, Emma L and de Groot, Lisette CPGM and Esko, Tonu and Gudnason, Vilmundar and Harris, Tamara B and Jackson, Rebecca D and Jukema, J Wouter and Ikram, Arfan MA and Karasik, David and Kaptoge, Stephen and Kung, Annie Wai Chee and Lehtim{\"a}ki, Terho and Lyytik{\"a}inen, Leo-Pekka and Lips, Paul and Luben, Robert and Metspalu, Andres and van Meurs, Joyce BJ and Minster, Ryan L and Orwoll, Erick and Oei, Edwin and Psaty, Bruce M and Raitakari, Olli T and Ralston, Stuart W and Ridker, Paul M and Robbins, John A and Smith, Albert V and Styrkarsdottir, Unnur and Tranah, Gregory J and Thorstensdottir, Unnur and Uitterlinden, Andre G and Zmuda, Joseph and Zillikens, M Carola and Ntzani, Evangelia E and Evangelou, Evangelos and Ioannidis, John PA and Evans, David M and Ohlsson, Claes and Pitsiladis, Yannis and Fuku, Noriyuki and Franks, Paul W and North, Kathryn N and van Duijn, Cornelia M and Mather, Karen A and Hansen, Torben and Hansson, Ola and Spector, Tim and Murabito, Joanne M and Richards, J Brent and Rivadeneira, Fernando and Langenberg, Claudia and Perry, John RB and Wareham, Nick J and Scott, Robert A},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {12},
  title        = {Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness},
  url          = {http://dx.doi.org/10.1038/ncomms16015},
  volume       = {8},
  year         = {2017},
}

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