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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
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,...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510175/ https://www.ncbi.nlm.nih.gov/pubmed/29313844 http://dx.doi.org/10.1038/ncomms16015 |
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| author | 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. 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. |
| author_facet | 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. 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. |
| author_sort | Willems, Sara M. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5510175 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-55101752017-07-17 Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness 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. 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. Nat Commun Article 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. Nature Publishing Group 2017-07-12 /pmc/articles/PMC5510175/ /pubmed/29313844 http://dx.doi.org/10.1038/ncomms16015 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| spellingShingle | Article 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. 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. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title_full | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title_fullStr | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title_full_unstemmed | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title_short | Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| title_sort | large-scale gwas identifies multiple loci for hand grip strength providing biological insights into muscular fitness |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510175/ https://www.ncbi.nlm.nih.gov/pubmed/29313844 http://dx.doi.org/10.1038/ncomms16015 |
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