دورية أكاديمية
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
| العنوان: | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
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| المؤلفون: | Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, JR, 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, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, I, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, D, McCarthy, MI, Pedersen, O, Khaw, K-T, Kiel, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA |
| بيانات النشر: | Nature Publishing Group //dx.doi.org/10.1038/ncomms16015 Nature Communications |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Actins, Adult, Aged, Cohort Studies, Female, Genetic Loci, Genetics, Population, Genome-Wide Association Study, Hand, Hand Strength, Humans, Male, Membrane Proteins, Middle Aged, Neoplasm Proteins, Nuclear Proteins, Polymorphism, Single Nucleotide, Repressor Proteins, Transforming Growth Factor alpha, United Kingdom, White People |
| الوصف: | 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. ; This research has been conducted using the UK Biobank Resource. The Fenland Study is supported by the UK Medical Research Council (MRC) (MC_UU_12015/1; MC_UU_12015/2; MC_UU_12015/3). EPIC-Norfolk is supported by the MRC (G401527, G1000143) and Cancer Research UK (A8257). The HCS is gratefully supported by the University of Newcastle (Australia) and the Fairfax Family Foundation. Sydney MAS is supported by the Australian National Health and Medical Research Council (NHMRC), grants ID568969, ID350833 and ID109308. Sydney MAS DNA was extracted by Genetic Repositories Australia, funded by NHMRC Enabling Grant 401184. The GEFOS Study, used as controls for the US and Jamaican athletes, was supported in part by NIH grants U01 HG004436 and P30 DK072488, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/264535Test |
| DOI: | 10.17863/CAM.9625 |
| الإتاحة: | https://doi.org/10.17863/CAM.9625Test https://www.repository.cam.ac.uk/handle/1810/264535Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.4DCB6D9C |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.9625 |
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