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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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 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
  • Cecilia M. Lindgren
  • Paul W. Franks
  • Ola Hansson
  • Thorvaldur Ingvarsson
  • GEFOS Anytype of Fracture Consortium
Organisations
External organisations
  • Johns Hopkins University School of Medicine
  • Skåne University Hospital
  • Guy's and St Thomas' NHS Foundation Trust
  • Hunter Medical Research Institute, Australia
  • Japan Society for the Promotion of Science
  • Glostrup Hospital
  • Slotervaart Hospital
  • Medical University of Gdansk
  • Ghent University
  • Copenhagen University Hospital
  • 12 de Octubre University Hospital
  • University of Cagliari
  • University of Glasgow
  • Victoria University
  • Umeå University
  • University of Akureyri
  • Akureyri Central Hospital
  • University of Cambridge
  • Erasmus University Medical Center
  • University of Edinburgh
  • McGill University
  • University of Queensland
  • University of Copenhagen
  • University of New South Wales
  • King's College London
  • Leiden University Medical Centre
  • Massachusetts General Hospital
  • Harvard Medical School
  • University of Brighton
  • University of California, San Diego
  • Stanford University
  • Broad Institute
  • Harvard University
  • Royal Children's Hospital, Melbourne
  • SmithKline Beecham Pharmaceuticals
  • Nottingham Trent University
  • University of Oxford
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Physiology
Original languageEnglish
Article number16015
JournalNature Communications
Volume8
Publication statusPublished - 2017 Jul 12
Publication categoryResearch
Peer-reviewedYes