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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 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; 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; Søren Brage; Yu-Ching Cheng; Paweł Cięszczyk; 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; Ian Varley; Louise V. Wain; Naomi R. Wray; Cecilia M. Lindgren; Daniel G. MacArthur; Dawn M. Waterworth; Mark I. McCarthy; Oluf Pedersen; Kay-Tee Khaw; Douglas P. Kiel; GEFOS Any-Type of Fracture Consortium; Yannis Pitsiladis; Noriyuki Fuku; Paul W. Franks; Kathryn N. North; Cornelia M. van Duijn; Karen A. Mather; Torben Hansen; Ola Hansson; Tim Spector; Joanne M. Murabito; J. Brent Richards; Fernando Rivadeneira; Claudia Langenberg; John R. B. Perry; Nick J. Wareham; Robert A. Scott

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 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
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
Søren Brage
Yu-Ching Cheng
Paweł Cięszczyk
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
Ian Varley
Louise V. Wain
Naomi R. Wray
Cecilia M. Lindgren
Daniel G. MacArthur
Dawn M. Waterworth
Mark I. McCarthy
Oluf Pedersen
Kay-Tee Khaw
Douglas P. Kiel
GEFOS Any-Type of Fracture Consortium
Yannis Pitsiladis
Noriyuki Fuku
Paul W. Franks
Kathryn N. North
Cornelia M. van Duijn
Karen A. Mather
Torben Hansen
Ola Hansson
Tim Spector
Joanne M. Murabito
J. Brent Richards
Fernando Rivadeneira
Claudia Langenberg
John R. B. Perry
Nick J. Wareham
Robert A. Scott
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/ncomms16015
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042717452
Tiivistelmä
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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