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DOI 10.1038/s41467-021-20918-w

Медицинская библиотека · Nature communications · 2021

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

Jones Garan, Trajanoska Katerina, Santanasto Adam J, Stringa Najada, Kuo Chia-Ling, Atkins Janice L, Lewis Joshua R, Duong ThuyVy, Hong Shengjun, Biggs Mary L, Luan Jian'an, Sarnowski Chloe, Lunetta Kathryn L, Tanaka Toshiko, Wojczynski Mary K, Cvejkus Ryan, Nethander Maria, Ghasemi Sahar, Yang Jingyun, Zillikens M Carola, Walter Stefan, Sicinski Kamil, Kague Erika, Ackert-Bicknell Cheryl L, Arking Dan E, Windham B Gwen, Boerwinkle Eric, Grove Megan L, Graff Misa, Spira Dominik, Demuth Ilja, van der Velde Nathalie, de Groot Lisette C P G M, Psaty Bruce M, Odden Michelle C, Fohner Alison E, Langenberg Claudia, Wareham Nicholas J, Bandinelli Stefania, van Schoor Natasja M, Huisman Martijn, Tan Qihua, Zmuda Joseph, Mellström Dan, Karlsson Magnus, Bennett David A, Buchman Aron S, De Jager Philip L, Uitterlinden Andre G, Völker Uwe, Kocher Thomas, Teumer Alexander, Rodriguéz-Mañas Leocadio, García Francisco J, Carnicero José A, Herd Pamela, Bertram Lars, Ohlsson Claes, Murabito Joanne M, Melzer David, Kuchel George A, Ferrucci Luigi, Karasik David, Rivadeneira Fernando, Kiel Douglas P, Pilling Luke C

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Аннотация

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.

Для цитирования: Jones Garan, Trajanoska Katerina, Santanasto Adam J, Stringa Najada, Kuo Chia-Ling, Atkins Janice L, Lewis Joshua R, Duong ThuyVy, Hong Shengjun, Biggs Mary L, Luan Jian'an, Sarnowski Chloe, Lunetta Kathryn L, Tanaka Toshiko, Wojczynski Mary K, Cvejkus Ryan, Nethander Maria, Ghasemi Sahar, Yang Jingyun, Zillikens M Carola, Walter Stefan, Sicinski Kamil, Kague Erika, Ackert-Bicknell Cheryl L, Arking Dan E, Windham B Gwen, Boerwinkle Eric, Grove Megan L, Graff Misa, Spira Dominik, Demuth Ilja, van der Velde Nathalie, de Groot Lisette C P G M, Psaty Bruce M, Odden Michelle C, Fohner Alison E, Langenberg Claudia, Wareham Nicholas J, Bandinelli Stefania, van Schoor Natasja M, Huisman Martijn, Tan Qihua, Zmuda Joseph, Mellström Dan, Karlsson Magnus, Bennett David A, Buchman Aron S, De Jager Philip L, Uitterlinden Andre G, Völker Uwe, Kocher Thomas, Teumer Alexander, Rodriguéz-Mañas Leocadio, García Francisco J, Carnicero José A, Herd Pamela, Bertram Lars, Ohlsson Claes, Murabito Joanne M, Melzer David, Kuchel George A, Ferrucci Luigi, Karasik David, Rivadeneira Fernando, Kiel Douglas P, Pilling Luke C. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.. Nature communications. 2021. DOI: 10.1038/s41467-021-20918-w.

Предметные рубрики MeSH

AgedAged, 80 and overAgingCohort StudiesEuropeFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGrowth Differentiation Factor 5HLA-DQ alpha-ChainsHumansMaleMiddle AgedMuscle StrengthMuscle WeaknessPolymorphism, Single NucleotideSarcopenia
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