Document Type

Journal Article

Publication Title

Nature Communications

Volume

12

Issue

1

Publisher

Springer Nature

School

School of Medical and Health Sciences

RAS ID

32712

Funders

UK Medical Research Council

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

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.

DOI

10.1038/s41467-021-20918-w

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Research Themes

Health

Priority Areas

Multidisciplinary biological approaches to personalised disease diagnosis, prognosis and management

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