03989nas a2201057 4500008004100000022001400041245012200055210006900177260001600246300001000262490000600272520101400278100002101292700002201313700001801335700002501353700002001378700002001398700002101418700002101439700001801460700002201478700002601500700002101526700001301547700001901560700001601579700001401595700001501609700002701624700002101651700001901672700002501691700002101716700001501737700001501752700001801767700001601785700001901801700001901820700002001839700001801859700002001877700002301897700001601920700002701936700001501963700002101978700002101999700002302020700002502043700002202068700002102090700002502111700002102136700002702157700002202184700001602206700002502222700002102247700001702268700002102285700001602306700002002322700001902342700002502361700002502386700002402411700002202435700001902457700001802476700002102494700002302515700001902538700002002557700002202577700002302599700002102622700001902643700001702662700001702679700002402696700002002720700002602740700002402766700002102790700002102811700002102832710004202853856003602895 2017 eng d a2041-172300aLarge-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.0 aLargescale GWAS identifies multiple loci for hand grip strength c2017 Jul 12 a160150 v83 a
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) 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.
1 aWillems, Sara, M1 aWright, Daniel, J1 aDay, Felix, R1 aTrajanoska, Katerina1 aJoshi, Peter, K1 aMorris, John, A1 aMatteini, Amy, M1 aGarton, Fleur, C1 aGrarup, Niels1 aOskolkov, Nikolay1 aThalamuthu, Anbupalam1 aMangino, Massimo1 aLiu, Jun1 aDemirkan, Ayse1 aLek, Monkol1 aXu, Liwen1 aWang, Guan1 aOldmeadow, Christopher1 aGaulton, Kyle, J1 aLotta, Luca, A1 aMiyamoto-Mikami, Eri1 aRivas, Manuel, A1 aWhite, Tom1 aLoh, Po-Ru1 aAadahl, Mette1 aAmin, Najaf1 aAttia, John, R1 aAustin, Krista1 aBenyamin, Beben1 aBrage, Søren1 aCheng, Yu-Ching1 aCięszczyk, Paweł1 aDerave, Wim1 aEriksson, Karl-Fredrik1 aEynon, Nir1 aLinneberg, Allan1 aLucia, Alejandro1 aMassidda, Myosotis1 aMitchell, Braxton, D1 aMiyachi, Motohiko1 aMurakami, Haruka1 aPadmanabhan, Sandosh1 aPandey, Ashutosh1 aPapadimitriou, Ioannis1 aRajpal, Deepak, K1 aSale, Craig1 aSchnurr, Theresia, M1 aSessa, Francesco1 aShrine, Nick1 aTobin, Martin, D1 aVarley, Ian1 aWain, Louise, V1 aWray, Naomi, R1 aLindgren, Cecilia, M1 aMacArthur, Daniel, G1 aWaterworth, Dawn, M1 aMcCarthy, Mark, I1 aPedersen, Oluf1 aKhaw, Kay-Tee1 aKiel, Douglas, P1 aPitsiladis, Yannis1 aFuku, Noriyuki1 aFranks, Paul, W1 aNorth, Kathryn, N1 aDuijn, Cornelia, M1 aMather, Karen, A1 aHansen, Torben1 aHansson, Ola1 aSpector, Tim1 aMurabito, Joanne, M1 aRichards, Brent1 aRivadeneira, Fernando1 aLangenberg, Claudia1 aPerry, John, R B1 aWareham, Nick, J1 aScott, Robert, A1 aGEFOS Any-Type of Fracture Consortium uhttps://chs-nhlbi.org/node/7688