Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.
复制标题
DOI：
10.1038/s41467-021-20918-w
复制
发表时间：
2021-01-28
影响因子：
16.6
通讯作者：
Pilling LC
中科院分区：
文献类型：
--
作者：
Jones G;Trajanoska K;Santanasto AJ;Stringa N;Kuo CL;Atkins JL;Lewis JR;Duong T;Hong S;Biggs ML;Luan J;Sarnowski C;Lunetta KL;Tanaka T;Wojczynski MK;Cvejkus R;Nethander M;Ghasemi S;Yang J;Zillikens MC;Walter S;Sicinski K;Kague E;Ackert-Bicknell CL;Arking DE;Windham BG;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
低肌肉力量是与老年人发病率和死亡率相关的健康状况不佳的一个重要遗传指标。在对来自22个队列的256，523名60岁及以上的欧洲人进行的全基因组关联研究荟萃分析中，我们确定了15个与肌无力相关的基因座（欧洲老年人肌肉减少症工作组定义：n = 48，596例，占总数的18.9%），包括12个与先前对握力连续测量的分析无关的基因座。据报道，基因座包括参与自身免疫性疾病（HLA-DQA 1 p = 4 × 10−17），关节炎（GDF 5 p = 4 × 10−13），细胞周期控制和癌症保护，转录调节以及其他参与肌肉骨骼系统发育和维持的基因。使用孟德尔随机化，我们报告了可能重叠的因果途径，包括糖尿病易感性，血液学参数和免疫系统。我们的结论是，老年人的肌肉无力有不同的机制，从持续的力量，包括几个途径被认为是衰老的标志。肌无力与老年人的发病率和死亡率有关。在这里，作者通过对握力和孟德尔随机化进行全基因组荟萃分析，进一步研究了这一特征，以发现肌无力与其他疾病之间的因果关系。
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.
登录
查看更多内容
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
DOI：
10.1161/01.atv.20.11.2386
发表时间：
2000-11-01
影响因子：
8.7
作者：
Herrmann, SM;Whatling, C;Cambien, F
通讯作者：
Cambien, F