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

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...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature communications Ročník 12; číslo 1; s. 654 - 11
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 28.01.2021 Nature Publishing Group Nature Portfolio
Témata:	45 45/43 631/208/205 631/208/212 692/308/2056 692/53/2423 Aged Aged, 80 and over Aging Aging - genetics Arthritis Autoimmune diseases Basic Medicine Cell cycle Clinical Medicine Cohort Studies Diabetes mellitus Europe Female Gene regulation Genetic Predisposition to Disease - genetics Genome-wide association studies Genome-Wide Association Study - methods Genomes Geriatrics Geriatrik Grip strength Growth Differentiation Factor 5 - genetics Histocompatibility antigen HLA HLA-DQ alpha-Chains - genetics Humanities and Social Sciences Humans Immune system Klinisk medicin Loci Male Medical and Health Sciences Medical Genetics and Genomics Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Men Meta-analysis Middle Aged Morbidity Mortality multidisciplinary Muscle strength Muscle Strength - genetics Muscle Strength - physiology Muscle Weakness - genetics Muscle Weakness - physiopathology Musculoskeletal system Older people Polymorphism, Single Nucleotide Randomization Sarcopenia Sarcopenia - genetics Sarcopenia - physiopathology Science Science & Technology - Other Topics Science (multidisciplinary) Transcription Europe
ISSN:	2041-1723, 2041-1723
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-20918-w