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

Sara M. Willems; Daniel J. Wright; Felix R. Day; Katerina Trajanoska; Peter K. Joshi; John A. Morris; Amy Matteini; Fleur C. Garton; Niels Grarup; Yannis Pitsiladis

doi:10.1038/ncomms16015

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

Sara M. Willems, Daniel J. Wright, Felix R. Day, Katerina Trajanoska, Peter K. Joshi, John A. Morris, Amy Matteini, Fleur C. Garton, Niels Grarup, Yannis Pitsiladis

Research output: Contribution to journal › Article › peer-review

Abstract

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 (Po5108) 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.

Original language	English
Article number	16015
Pages (from-to)	1-12
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms16015
Publication status	Published - 12 Jul 2017

Bibliographical note

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/

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Yannis Pitsiladis
- Y.Pitsiladis@brighton.ac.uk
- School of Sport and Service Management - Professor of Sport and Exercise Science
- Centre for Stress and Age-Related Disease
- Sport and Exercise Science and Sports Medicine Research and Enterprise Group
Person: Academic

Cite this

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

abstract = "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 (Po5108) 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.",

author = "Willems, {Sara M.} and Wright, {Daniel J.} and Day, {Felix R.} and Katerina Trajanoska and Joshi, {Peter K.} and Morris, {John A.} and Amy Matteini and Garton, {Fleur C.} and Niels Grarup and Yannis Pitsiladis",

note = "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{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}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/",

year = "2017",

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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; Garton, Fleur C.; Grarup, Niels; Pitsiladis, Yannis.

In: Nature Communications, Vol. 8, 16015, 12.07.2017, p. 1-12.

Research output: Contribution to journal › Article › peer-review

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AU - Garton, Fleur C.

AU - Grarup, Niels

AU - Pitsiladis, Yannis

N1 - 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/

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N2 - 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 (Po5108) 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.

AB - 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 (Po5108) 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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