Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
Yu-Ching Cheng; Nikolay Oskolkov; Noriyuki Fuku; Luca A. Lotta; Robert A. Scott; Dawn M. Waterworth; Oluf Pedersen; Daniel G. MacArthur; Douglas P. Kiel; Daniel J. Wright; Niels Grarup; Craig Sale; Ayse Demirkan; Guan Wang; Wim Derave; Najaf Amin; Torben Hansen; Liwen Xu; Deepak K. Rajpal; Claudia Langenberg; Tom White; Sara M. Willems; Christopher Oldmeadow; Monkol Lek; Haruka Murakami; Ashutosh Pandey; Sandosh Padmanabhan; Krista Austin; Kay-Tee Khaw; Paweł Cięszczyk; Louise V. Wain; Beben Benyamin; Kathryn N. North; Alejandro Lucia; Joanne M. Murabito; Cecilia M. Lindgren; Francesco Sessa; Allan Linneberg; Jun Liu; Anbupalam Thalamuthu; Nir Eynon; Cornelia M. van Duijn; John R. B. Perry; Braxton D. Mitchell; Ioannis Papadimitriou; Peter K. Joshi; Theresia M. Schnurr; GEFOS Any-Type of Fracture Consortium; Søren Brage; Myosotis Massidda; Tim Spector; Ian Varley; Yannis Pitsiladis; Massimo Mangino; Nick J. Wareham; J. Brent Richards; Martin D. Tobin; Fernando Rivadeneira; Paul W. Franks; Fleur C. Garton; Kyle J. Gaulton; Nick Shrine; Karen A. Mather; Manuel A. Rivas; Karl-Fredrik Eriksson; Felix R. Day; John R. Attia; Katerina Trajanoska; Amy M. Matteini; Eri Miyamoto-Mikami; Ola Hansson; John A. Morris; Motohiko Miyachi; Mette Aadahl; Naomi R. Wray; Po-Ru Loh; Mark I. McCarthy
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042717452
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.
Kokoelmat
- Rinnakkaistallenteet [19207]