Abstract
© 2021, The Author(s). Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256, 523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
Keywords
genome-wide meta-analysis, muscle weakness, susceptibility loci, older men, older women, muscle strength, ageing
Document Type
Journal Article
Date of Publication
2021
Volume
12
Issue
1
Publication Title
Nature Communications
Publisher
Springer Nature
School
School of Medical and Health Sciences
RAS ID
32712
Funders
UK Medical Research Council
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Jones, G., Trajanoska, K., Santanasto, A. J., Stringa, N., Kuo, C. L., Atkins, J. L., ... Pilling, L. C. (2021). Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nature Communications, 12, article number 654. https://doi.org/10.1038/s41467-021-20918-w