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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Published version
Peer-reviewed

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Authors

Trajanoska, Katerina  ORCID logo  https://orcid.org/0000-0002-3792-4296
Santanasto, Adam J.  ORCID logo  https://orcid.org/0000-0002-6912-2909
Kuo, Chia-Ling 

Abstract

Abstract: 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.

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Keywords

Article, /631/208/205, /631/208/212, /692/53/2423, /692/308/2056, /45, /45/43, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

12

Publisher

Nature Publishing Group UK
Sponsorship
RCUK | Medical Research Council (MRC) (MR/M023095/1)