Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
Nature communications 2020 ; 12: 654.
Jones G, Trajanoska K, Santanasto AJ, Stringa N, Kuo CL, Atkins JL, Lewis JR, Duong T, Hong S, Biggs ML, Luan J, Sarnowski C, Lunetta KL, Tanaka T, Wojczynski MK, Cvejkus R, Nethander M, Ghasemi S, Yang J, Zillikens MC, Walter S, Sicinski K, Kague E, Ackert-Bicknell CL, Arking DE, Windham BG, Boerwinkle E, Grove ML, Graff M, Spira D, Demuth I, van der Velde N, de Groot LCPGM, Psaty BM, Odden MC, Fohner AE, Langenberg C, Wareham NJ, Bandinelli S, van Schoor NM, Huisman M, Tan Q, Zmuda J, Mellström D, Karlsson M, Bennett DA, Buchman AS, De Jager PL, Uitterlinden AG, Völker U, Kocher T, Teumer A, Rodriguéz-Mañas L, García FJ, Carnicero JA, Herd P, Bertram L, Ohlsson C, Murabito JM, Melzer D, Kuchel GA, Ferrucci L, Karasik D, Rivadeneira F, Kiel DP, and Pilling LC
DOI : 10.1038/s41467-021-20918-w
PubMed ID : 33510174
PMCID : PMC7844411
URL : https://www.nature.com/articles/s41467-021-20918-w
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-DQA1 p = 4 × 10), arthritis (GDF5 p = 4 × 10), 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.