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; 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; GEFOS Any-Type of Fracture Consortium

doi:10.1038/ncomms16015

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

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.8(1), pp.16015-16015

12/07/2017

DOI: https://doi.org/10.1038/ncomms16015

PMID: 29313844

Abstract

Actins - genetics

Adult

Aged

Cohort Studies

Female

Genetic Loci

Genetics, Population

Genome-Wide Association Study

Hand - physiology

Hand Strength

Humans

Male

Membrane Proteins - genetics

Middle Aged

Neoplasm Proteins - genetics

Nuclear Proteins - genetics

Polymorphism, Single Nucleotide

Repressor Proteins - genetics

Transforming Growth Factor alpha - genetics

United Kingdom

White People - genetics

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 ) 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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Title: Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
Creators: Sara M Willems - University of Cambridge
Daniel J Wright - MRC Epidemiology Unit
Felix R Day - MRC Epidemiology Unit
Katerina Trajanoska - Erasmus MC
Peter K Joshi - University of Edinburgh
John A Morris - Jewish General Hospital
Amy M Matteini - Johns Hopkins Medicine
Fleur C Garton - University of Queensland
Niels Grarup - Novo Nordisk Foundation
Nikolay Oskolkov - Lund University
Anbupalam Thalamuthu - UNSW Sydney
Massimo Mangino - King's College London
Jun Liu - Erasmus MC
Ayse Demirkan - Erasmus MC
Monkol Lek - Massachusetts General Hospital
Liwen Xu - Harvard Medical School
Guan Wang - University of Brighton
Christopher Oldmeadow - Hunter Medical Research Institute
Kyle J Gaulton - University of California, San Diego
Luca A Lotta - MRC Epidemiology Unit
Eri Miyamoto-Mikami - Department of Sports and Life Science, National Institute of Fitness and Sports, Kanoya, Kagoshima 891-2393, Japan
Manuel A Rivas - Stanford University
Tom White - MRC Epidemiology Unit
Po-Ru Loh - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA
Mette Aadahl - Glostrup Hospital
Najaf Amin - Erasmus MC
John R Attia - Hunter Medical Research Institute
Krista Austin - University of Brighton
Beben Benyamin - University of Queensland
Søren Brage - University of Cambridge
Yu-Ching Cheng - Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
Paweł Cięszczyk - Gdansk University of Physical Education and Sport
Wim Derave - Ghent University
Karl-Fredrik Eriksson - Lund University
Nir Eynon - Victoria University
Allan Linneberg - Glostrup Hospital
Alejandro Lucia - Universidad Europea de Madrid
Myosotis Massidda - University of Cagliari
Braxton D Mitchell - University of Maryland, Baltimore
Motohiko Miyachi - National Institute of Biomedical Innovation, Health and Nutrition
Haruka Murakami - National Institute of Biomedical Innovation, Health and Nutrition
Sandosh Padmanabhan - University of Glasgow
Ashutosh Pandey - Target
Ioannis Papadimitriou - Victoria University
Deepak K Rajpal - GlaxoSmithKline
Craig Sale - Nottingham Trent University
Theresia M Schnurr - Novo Nordisk Foundation
Francesco Sessa - University of Foggia
Nick Shrine - University of Leicester
Martin D Tobin - University of Leicester
Ian Varley - Nottingham Trent University
Louise V Wain - University of Leicester
Naomi R Wray - University of Queensland
Cecilia M Lindgren - Broad Institute
Daniel G MacArthur - Massachusetts General Hospital
Dawn M Waterworth - GlaxoSmithKline
Mark I McCarthy - Wellcome Centre for Human Genetics
Oluf Pedersen - University of Copenhagen
Kay-Tee Khaw - University of Cambridge
Douglas P Kiel - Harvard University
Yannis Pitsiladis - University of Brighton
Noriyuki Fuku - Juntendo University
Paul W Franks - Umeå University
Kathryn N North - Royal Children's Hospital
Cornelia M van Duijn - Erasmus MC
Karen A Mather - UNSW Sydney
Torben Hansen - University of Southern Denmark
Ola Hansson - Lund University
Tim Spector - King's College London
Joanne M Murabito - Framingham Heart Study
J Brent Richards - McGill University
Fernando Rivadeneira - Erasmus MC
Claudia Langenberg - University of Cambridge
John R B Perry - University of Cambridge
Nick J Wareham - University of Cambridge
Robert A Scott - University of Cambridge
GEFOS Any-Type of Fracture Consortium
Publication Details: Nature communications, Vol.8(1), pp.16015-16015
Date published: 12/07/2017
Grant note: G0401527 / Medical Research Council P30 DK048520 / NIDDK NIH HHS MR/N003284/1 / Medical Research Council U24 AG051129 / NIA NIH HHS MC_UU_12015/1 / Medical Research Council MR/N011317/1 / Medical Research Council R01 HL105756 / NHLBI NIH HHS MC_UU_12015/2 / Medical Research Council MC_QA137853 / Medical Research Council MC_U106179473 / Medical Research Council
Identifiers: 99928600602346
Academic Unit: Institute for Sustainability; Surrey Institute for People-Centred AI; School of Biosciences
Language: English
Resource Type: Journal article

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

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