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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
Willems, Sara M. Wright, Daniel J. Day, Felix R. Trajanoska, Katerina Joshi, Peter K. Morris, John A. Matteini, Amy M. Garton, Fleur C. Grarup, Niels Oskolkov, Nikolay
Willems, Sara M.
Wright, Daniel J.
Day, Felix R.
Trajanoska, Katerina
Joshi, Peter K.
Morris, John A.
Matteini, Amy M.
Garton, Fleur C.
Grarup, Niels
Oskolkov, Nikolay
Author
Willems, Sara M.
Wright, Daniel J.
Day, Felix R.
Trajanoska, Katerina
Joshi, Peter K.
Morris, John A.
Matteini, Amy M.
Garton, Fleur C.
Grarup, Niels
Oskolkov, Nikolay
Thalamuthu, Anbupalam
Mangino, Massimo
Liu, Jun
Demirkan, Ayse
Lek, Monkol
Xu, Liwen
Wang, Guan
Oldmeadow, Christopher
Gaulton, Kyle J.
Lotta, Luca A.
Miyamoto-Mikami, Eri
Rivas, Manuel A.
White, Tom
Loh, Po-Ru
Aadahl, Mette
Amin, Najaf
Attia, John R.
Austin, Krista
Benyamin, Beben
Wright, Daniel J.
Day, Felix R.
Trajanoska, Katerina
Joshi, Peter K.
Morris, John A.
Matteini, Amy M.
Garton, Fleur C.
Grarup, Niels
Oskolkov, Nikolay
Thalamuthu, Anbupalam
Mangino, Massimo
Liu, Jun
Demirkan, Ayse
Lek, Monkol
Xu, Liwen
Wang, Guan
Oldmeadow, Christopher
Gaulton, Kyle J.
Lotta, Luca A.
Miyamoto-Mikami, Eri
Rivas, Manuel A.
White, Tom
Loh, Po-Ru
Aadahl, Mette
Amin, Najaf
Attia, John R.
Austin, Krista
Benyamin, Beben
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.
Keywords
Date
2017
Type
Journal article
Journal
Nature Communications
Book
Volume
8
Issue
1
Page Range
1-12
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open
Notes
Please refer to the full article for a complete list of author names.