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Nature Research, Nature Communications, 1(12), 2021

DOI: 10.1038/s41467-021-20918-w



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

Journal article published in 2021 by Garan Jones ORCID, Katerina Trajanoska ORCID, Adam J. Santanasto ORCID, Najada Stringa ORCID, Chia-Ling Kuo, Janice L. Atkins ORCID, Joshua R. Lewis ORCID, ThuyVy Duong, Shengjun Hong, Mary L. Biggs, Jian’an Luan ORCID, Chloe Sarnowski ORCID, Kathryn L. Lunetta ORCID, Toshiko Tanaka, Mary K. Wojczynski and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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AbstractLow 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.