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

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

in 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

2021

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

2021

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2021

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Journal Article

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

Luan, Jian’an,

Fohner, Alison E.,

Windham, B. Gwen,

Buchman, Aron S.,

Jones, Garan,

Psaty, Bruce M.,

Herd, Pamela,

Kuo, Chia-Ling,

Walter, Stefan,

Cvejkus, Ryan,

Grove, Megan L.,

Rivadeneira, Fernando,

Völker, Uwe,

Pilling, Luke C.,

Tanaka, Toshiko,

García, Francisco J.,

Duong, ThuyVy,

Bertram, Lars,

Wojczynski, Mary K.,

Demuth, Ilja,

Wareham, Nicholas J.,

Murabito, Joanne M.,

Arking, Dan E.,

Lewis, Joshua R.,

Uitterlinden, Andre G.,

Spira, Dominik,

Tan, Qihua,

Stringa, Najada,

van der Velde, Nathalie,

Karlsson, Magnus,

Kiel, Douglas P.,

Zmuda, Joseph,

Yang, Jingyun,

de Groot, Lisette C. P. G. M.,

Kuchel, George A.,

Sicinski, Kamil,

Langenberg, Claudia,

Boerwinkle, Eric,

Odden, Michelle C.,

Zillikens, M. Carola,

Melzer, David,

Trajanoska, Katerina,

Lunetta, Kathryn L.,

Sarnowski, Chloe,

Ackert-Bicknell, Cheryl L.,

Mellström, Dan,

Ferrucci, Luigi,

Carnicero, José A.,

Bandinelli, Stefania,

van Schoor, Natasja M.,

Huisman, Martijn,

Ghasemi, Sahar,

Bennett, David A.,

Kague, Erika,

Santanasto, Adam J.,

Teumer, Alexander,

Biggs, Mary L.,

Graff, Misa,

Rodriguéz-Mañas, Leocadio,

Ohlsson, Claes,

Hong, Shengjun,

2021

Overview

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.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

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