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

Nat Commun
Authors
Sara Willems
Daniel Wright
Felix Day
Katerina Trajanoska
Peter Joshi
John Morris
Amy Matteini
Fleur Garton
Niels Grarup
Nikolay Oskolkov
Anbupalam Thalamuthu
Massimo Mangino
Jun Liu
Ayse Demirkan
Monkol Lek
Liwen Xu
Guan Wang
Christopher Oldmeadow
Kyle Gaulton
Luca Lotta
Eri Miyamoto-Mikami
Manuel Rivas
Tom White
Po-Ru Loh
Mette Aadahl
Najaf Amin
John 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 Mitchell
Motohiko Miyachi
Haruka Murakami
Sandosh Padmanabhan
Ashutosh Pandey
Ioannis Papadimitriou
Deepak Rajpal
Craig Sale
Theresia Schnurr
Francesco Sessa
Nick Shrine
Martin Tobin
Ian Varley
Louise Wain
Naomi Wray
Cecilia Lindgren
Daniel MacArthur
Dawn Waterworth
Mark McCarthy
Oluf Pedersen
Kay-Tee Khaw
Douglas Kiel
GEFOS Any-Type of Fracture Consortium
Yannis Pitsiladis
Noriyuki Fuku
Paul Franks
Kathryn North
Cornelia van Duijn
Karen Mather
Torben Hansen
Ola Hansson
Tim Spector
Joanne Murabito
J Brent Richards
Fernando Rivadeneira
Claudia Langenberg
John Perry
Nick Wareham
Robert Scott
Keywords
Female
Humans
Male
Adult
Aged
Neoplasm Proteins
Middle Aged
Cohort Studies
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Nuclear Proteins
Repressor Proteins
European Continental Ancestry Group
Membrane Proteins
Genetic Loci
Genetics, Population
Actins
United Kingdom
Hand
Hand Strength
Transforming Growth Factor alpha
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 (P5 × 10) 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.
Year of Publication
2017
Journal
Nat Commun
Volume
8
Pages
16015
Date Published
2017 07 12
ISSN
2041-1723
DOI
10.1038/ncomms16015
PubMed ID
29313844
PubMed Central ID
PMC5510175
Links
Grant list
P30 DK048520 / DK / NIDDK NIH HHS / United States
MR/N003284/1 / MRC_ / Medical Research Council / United Kingdom
G1000143 / MRC_ / Medical Research Council / United Kingdom
MC_U106179473 / MRC_ / Medical Research Council / United Kingdom
R01 AR041398 / AR / NIAMS NIH HHS / United States
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
P30 DK072488 / DK / NIDDK NIH HHS / United States
G0401527 / MRC_ / Medical Research Council / United Kingdom
U24 AG051129 / AG / NIA NIH HHS / United States
WT_ / Wellcome Trust / United Kingdom
R21 AR056405 / AR / NIAMS NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
MR/N011317/1 / MRC_ / Medical Research Council / United Kingdom
UL1 TR002369 / TR / NCATS NIH HHS / United States
MC_UU_12015/3 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
G0902313 / MRC_ / Medical Research Council / United Kingdom
U01 HG004436 / HG / NHGRI NIH HHS / United States

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