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

doi:10.1038/ncomms16015

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Willems, Sara M. (author)

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

E-article/E-chapterEnglish2017

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Nature Publishing Group2017

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LIBRIS-ID:20912012
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-137942uri
urn:nbn:se:umu:diva-137942urn
10.1038/ncomms16015doi

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Language:English

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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.

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Wright, Daniel J. (author)
Day, Felix R. (author)
Trajanoska, Katerina (author)
Joshi, Peter K. (author)
Morris, John A. (author)
Matteini, Amy M. (author)
Garton, Fleur C. (author)
Grarup, Niels (author)
Oskolkov, Nikolay (author)
Thalamuthu, Anbupalam (author)
Mangino, Massimo (author)
Liu, Jun (author)
Demirkan, Ayse (author)
Lek, Monkol (author)
Xu, Liwen (author)
Wang, Guan (author)
Oldmeadow, Christopher (author)
Gaulton, Kyle J. (author)
Lotta, Luca A. (author)
Miyamoto-Mikami, Eri (author)
Rivas, Manuel A. (author)
White, Tom (author)
Loh, Po-Ru (author)
Aadahl, Mette (author)
Amin, Najaf (author)
Attia, John R. (author)
Austin, Krista (author)
Benyamin, Beben (author)
Brage, Soren (author)
Cheng, Yu-Ching (author)
Cieszczyk, Pawel (author)
Derave, Wim (author)
Eriksson, Karl-Fredrik (author)
Eynon, Nir (author)
Linneberg, Allan (author)
Lucia, Alejandro (author)
Massidda, Myosotis (author)
Mitchell, Braxton D. (author)
Miyachi, Motohiko (author)
Murakami, Haruka (author)
Padmanabhan, Sandosh (author)
Pandey, Ashutosh (author)
Papadimitriou, Loannis (author)
Rajpal, Deepak K. (author)
Sale, Craig (author)
Schnurr, Theresia M. (author)
Sessa, Francesco (author)
Shrine, Nick (author)
Tobin, Martin D. (author)
Varley, Ian (author)
Wain, Louise V. (author)
Wray, Naomi R. (author)
Lindgren, Cecilia M. (author)
MacArthur, Daniel G. (author)
Waterworth, Dawn M. (author)
McCarthy, Mark I. (author)
Pedersen, Oluf (author)
Khaw, Kay-Tee (author)
Kie, Douglas P. (author)
Pitsiladis, Yannis (author)
Fuku, Noriyuki (author)
Franks, Paul W. (author)
North, Kathryn N. (author)
van Duijn, Cornelia M. (author)
Mather, Karen A. (author)
Hansen, Torben (author)
Hansson, Ola (author)
Spector, Tim (author)
Murabito, Joanne M. (author)
Richards, J. Brent (author)
Rivadeneira, Fernando (author)
Langenberg, Claudia (author)
Perry, John R. B. (author)
Wareham, Nick J. (author)
Scott, Robert A. (author)
Umeå universitetMedicinska fakulteten268483 (publisher)
Umeå universitetMedicinska fakulteten268483 (publisher)

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In:VärdpublikationNature Communications82041-1723

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By the author/editor: Willems, Sara M.; Wright, Daniel J ...; Day, Felix R.; Trajanoska, Kate ...; Joshi, Peter K.; Morris, John A.; show more...; Matteini, Amy M.; Garton, Fleur C.; Grarup, Niels; Oskolkov, Nikola ...; Thalamuthu, Anbu ...; Mangino, Massimo; Liu, Jun; Demirkan, Ayse; Lek, Monkol; Xu, Liwen; Wang, Guan; Oldmeadow, Chris ...; Gaulton, Kyle J.; Lotta, Luca A.; Miyamoto-Mikami, ...; Rivas, Manuel A.; White, Tom; Loh, Po-Ru; Aadahl, Mette; Amin, Najaf; Attia, John R.; Austin, Krista; Benyamin, Beben; Brage, Soren; Cheng, Yu-Ching; Cieszczyk, Pawel; Derave, Wim; Eriksson, Karl-F ...; Eynon, Nir; Linneberg, Allan; Lucia, Alejandro; Massidda, Myosot ...; Mitchell, Braxto ...; Miyachi, Motohik ...; Murakami, Haruka; Padmanabhan, San ...; Pandey, Ashutosh; Papadimitriou, L ...; Rajpal, Deepak K ...; Sale, Craig; Schnurr, Theresi ...; Sessa, Francesco; Shrine, Nick; Tobin, Martin D.; Varley, Ian; Wain, Louise V.; Wray, Naomi R.; Lindgren, Cecili ...; MacArthur, Danie ...; Waterworth, Dawn ...; McCarthy, Mark I ...; Pedersen, Oluf; Khaw, Kay-Tee; Kie, Douglas P.; Pitsiladis, Yann ...; Fuku, Noriyuki; Franks, Paul W.; North, Kathryn N ...; van Duijn, Corne ...; Mather, Karen A.; Hansen, Torben; Hansson, Ola; Spector, Tim; Murabito, Joanne ...; Richards, J. Bre ...; Rivadeneira, Fer ...; Langenberg, Clau ...; Perry, John R. B ...; Wareham, Nick J.; Scott, Robert A.; show less...

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