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

TitleGenome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
Publication TypeJournal Article
Year of Publication2021
AuthorsJones, G, Trajanoska, K, Santanasto, AJ, Stringa, N, Kuo, C-L, Atkins, JL, Lewis, JR, Duong, TV, Hong, S, Biggs, ML, Luan, J'an, Sarnowski, C, Lunetta, KL, Tanaka, T, Wojczynski, MK, Cvejkus, R, Nethander, M, Ghasemi, S, Yang, J, M Zillikens, C, Walter, S, Sicinski, K, Kague, E, Ackert-Bicknell, CL, Arking, DE, B Windham, G, 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, Pilling, LC
JournalNat Commun
Volume12
Issue1
Pagination654
Date Published2021 01 28
ISSN2041-1723
KeywordsAged, Aged, 80 and over, Aging, Cohort Studies, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Growth Differentiation Factor 5, HLA-DQ alpha-Chains, Humans, Male, Middle Aged, Muscle Strength, Muscle Weakness, Polymorphism, Single Nucleotide, Sarcopenia
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-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.

DOI10.1038/s41467-021-20918-w
Alternate JournalNat Commun
PubMed ID33510174
PubMed Central IDPMC7844411
Grant ListR01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
MR/M008924/1 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00006/1 / MRC_ / Medical Research Council / United Kingdom
MR/M023095/1 / MRC_ / Medical Research Council / United Kingdom
K01 AG057726 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States