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

GEFOS Anytype of Fracture Consortium, Sara M. Willems, Daniel J. Wright, Felix R. Day, Katerina Trajanoska, Peter K. Joshi, John A. Morris, Amy M. Matteini, Fleur C. Garton, Niels Grarup, Nikolay Oskolkov, Anbupalam Thalamuthu, Massimo Mangino, Jun Liu, Ayse Demirkan, Monkol Lek, Liwen Xu, Guan Wang, Christopher Oldmeadow, Kyle J. Gaulton & 30 others Luca A. Lotta, Eri Miyamoto-Mikami, Manuel A. Rivas, Tom White, Po Ru Loh, Mette Aadahl, Najaf Amin, John R. Attia, Krista Austin, Beben Benyamin, Yu Ching Cheng, Paweł Ciȩszczyk, Wim Derave, Karl Fredrik Eriksson, Nir Eynon, Allan Linneberg, Alejandro Lucia, Myosotis Massidda, Braxton D. Mitchell, Motohiko Miyachi, Haruka Murakami, Sandosh Padmanabhan, Ashutosh Pandey, Ioannis Papadimitriou, Deepak K. Rajpal, Craig Sale, Theresia M. Schnurr, Francesco Sessa, Nick Shrine, Martin D. Tobin

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 (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.

LanguageEnglish
Article number16015
JournalNature communications
Volume8
DOIs
Publication statusPublished - 12 Jul 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

@article{785a483fa219497daf1262a81ca140d5,
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 (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.",
author = "{GEFOS Anytype of Fracture Consortium} and Willems, {Sara M.} and Wright, {Daniel J.} and Day, {Felix R.} and Katerina Trajanoska and Joshi, {Peter K.} and Morris, {John A.} and Matteini, {Amy M.} and Garton, {Fleur C.} and Niels Grarup and Nikolay Oskolkov and Anbupalam Thalamuthu and Massimo Mangino and Jun Liu and Ayse Demirkan and Monkol Lek and Liwen Xu and Guan Wang and Christopher Oldmeadow and Gaulton, {Kyle J.} and Lotta, {Luca A.} and Eri Miyamoto-Mikami and Rivas, {Manuel A.} and Tom White and Loh, {Po Ru} and Mette Aadahl and Najaf Amin and Attia, {John R.} and Krista Austin and Beben Benyamin and Cheng, {Yu Ching} and Paweł Ciȩszczyk and Wim Derave and Eriksson, {Karl Fredrik} and Nir Eynon and Allan Linneberg and Alejandro Lucia and Myosotis Massidda and Mitchell, {Braxton D.} and Motohiko Miyachi and Haruka Murakami and Sandosh Padmanabhan and Ashutosh Pandey and Ioannis Papadimitriou and Rajpal, {Deepak K.} and Craig Sale and Schnurr, {Theresia M.} and Francesco Sessa and Nick Shrine and Tobin, {Martin D.}",
year = "2017",
month = "7",
day = "12",
doi = "10.1038/ncomms16015",
language = "English",
volume = "8",
journal = "Nature Communications",
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. / GEFOS Anytype of Fracture Consortium.

In: Nature communications, Vol. 8, 16015, 12.07.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

AU - GEFOS Anytype of Fracture Consortium

AU - Willems, Sara M.

AU - Wright, Daniel J.

AU - Day, Felix R.

AU - Trajanoska, Katerina

AU - Joshi, Peter K.

AU - Morris, John A.

AU - Matteini, Amy M.

AU - Garton, Fleur C.

AU - Grarup, Niels

AU - Oskolkov, Nikolay

AU - Thalamuthu, Anbupalam

AU - Mangino, Massimo

AU - Liu, Jun

AU - Demirkan, Ayse

AU - Lek, Monkol

AU - Xu, Liwen

AU - Wang, Guan

AU - Oldmeadow, Christopher

AU - Gaulton, Kyle J.

AU - Lotta, Luca A.

AU - Miyamoto-Mikami, Eri

AU - Rivas, Manuel A.

AU - White, Tom

AU - Loh, Po Ru

AU - Aadahl, Mette

AU - Amin, Najaf

AU - Attia, John R.

AU - Austin, Krista

AU - Benyamin, Beben

AU - Cheng, Yu Ching

AU - Ciȩszczyk, Paweł

AU - Derave, Wim

AU - Eriksson, Karl Fredrik

AU - Eynon, Nir

AU - Linneberg, Allan

AU - Lucia, Alejandro

AU - Massidda, Myosotis

AU - Mitchell, Braxton D.

AU - Miyachi, Motohiko

AU - Murakami, Haruka

AU - Padmanabhan, Sandosh

AU - Pandey, Ashutosh

AU - Papadimitriou, Ioannis

AU - Rajpal, Deepak K.

AU - Sale, Craig

AU - Schnurr, Theresia M.

AU - Sessa, Francesco

AU - Shrine, Nick

AU - Tobin, Martin D.

PY - 2017/7/12

Y1 - 2017/7/12

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 (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.

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 (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.

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U2 - 10.1038/ncomms16015

DO - 10.1038/ncomms16015

M3 - Article

VL - 8

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 16015

ER -