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 identified 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, hematological 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.

中文翻译：

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全基因组的肌无力荟萃分析确定了老年男性和女性的15个易感基因座

肌肉力量低下是与老年人的发病率和死亡率相关的健康状况不佳的重要遗传指标。在全基因组关联研究的荟萃分析中，对来自22个队列的256,523名60岁及以上的欧洲人进行了分析，我们确定了15个与肌肉无力相关的基因座（欧洲老年人肌肉结节病工作组定义：n = 48,596例，占总数的18.9％） ，包括12个基因座，这些基因座在以前对抓握强度连续测量的分析中没有涉及。基因座包括据报道参与自身免疫性疾病（HLA-DQA1 p = 4 * 10-17），关节炎（GDF5 p = 4 * 10-13），细胞周期控制和癌症保护，转录调控及其他与发育有关的基因和维护肌肉骨骼系统。使用孟德尔随机法，我们报告了可能的重叠因果路径，包括糖尿病易感性，血液学参数和免疫系统。我们得出的结论是，老年人的肌肉无力具有与持续强度不同的机制，包括被认为是衰老的几种途径。