| Literature DB >> 33510174 |
Garan Jones1, Katerina Trajanoska2,3, Adam J Santanasto4, Najada Stringa5, Chia-Ling Kuo6, Janice L Atkins1, Joshua R Lewis7,8,9, ThuyVy Duong10, Shengjun Hong11, Mary L Biggs12, Jian'an Luan13, Chloe Sarnowski14, Kathryn L Lunetta14, Toshiko Tanaka15, Mary K Wojczynski16, Ryan Cvejkus4, Maria Nethander17,18, Sahar Ghasemi19,20, Jingyun Yang21, M Carola Zillikens2, Stefan Walter22,23, Kamil Sicinski24, Erika Kague25, Cheryl L Ackert-Bicknell26, Dan E Arking10, B Gwen Windham27, Eric Boerwinkle28,29, Megan L Grove28, Misa Graff30, Dominik Spira31,32, Ilja Demuth31,32,33, Nathalie van der Velde34, Lisette C P G M de Groot35, Bruce M Psaty36,37, Michelle C Odden38, Alison E Fohner39, Claudia Langenberg13, Nicholas J Wareham13, Stefania Bandinelli40, Natasja M van Schoor5, Martijn Huisman5, Qihua Tan41, Joseph Zmuda4, Dan Mellström17,42, Magnus Karlsson43, David A Bennett21, Aron S Buchman21, Philip L De Jager44,45, Andre G Uitterlinden2, Uwe Völker46, Thomas Kocher47, Alexander Teumer20, Leocadio Rodriguéz-Mañas23,48, Francisco J García23,49, José A Carnicero23, Pamela Herd50, Lars Bertram11, Claes Ohlsson17,51, Joanne M Murabito52, David Melzer1, George A Kuchel53, Luigi Ferrucci54, David Karasik55,56, Fernando Rivadeneira2,3, Douglas P Kiel57, Luke C Pilling58.
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 × 10-17), arthritis (GDF5 p = 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.Entities:
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Year: 2021 PMID： 33510174 PMCID： PMC7844411 DOI： 10.1038/s41467-021-20918-w
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919