Nature communications · 2017

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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Willems Sara M, Wright Daniel J, Day Felix R, Trajanoska Katerina, Joshi Peter K, Morris John A, Matteini Amy M, Garton Fleur C, Grarup Niels, Oskolkov Nikolay, Thalamuthu Anbupalam, Mangino Massimo, Liu Jun, Demirkan Ayse, Lek Monkol, Xu Liwen, Wang Guan, Oldmeadow Christopher, Gaulton Kyle J, Lotta Luca A, Miyamoto-Mikami Eri, Rivas Manuel A, White Tom, Loh Po-Ru, Aadahl Mette, Amin Najaf, Attia John R, Austin Krista, Benyamin Beben, Brage Søren, Cheng Yu-Ching, Cięszczyk Paweł, Derave Wim, Eriksson Karl-Fredrik, Eynon Nir, Linneberg Allan, Lucia Alejandro, Massidda Myosotis, Mitchell Braxton D, Miyachi Motohiko, Murakami Haruka, Padmanabhan Sandosh, Pandey Ashutosh, Papadimitriou Ioannis, Rajpal Deepak K, Sale Craig, Schnurr Theresia M, Sessa Francesco, Shrine Nick, Tobin Martin D, Varley Ian, Wain Louise V, Wray Naomi R, Lindgren Cecilia M, MacArthur Daniel G, Waterworth Dawn M, McCarthy Mark I, Pedersen Oluf, Khaw Kay-Tee, Kiel Douglas P, GEFOS Any-Type of Fracture Consortium, Pitsiladis Yannis, Fuku Noriyuki, Franks Paul W, North Kathryn N, van Duijn Cornelia M, Mather Karen A, Hansen Torben, Hansson Ola, Spector Tim, Murabito Joanne M, Richards J Brent, Rivadeneira Fernando, Langenberg Claudia, Perry John R B, Wareham Nick J, Scott Robert A

Аннотация

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.

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

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