Chen Chunlan, He Ying
Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Genet. 2024 Apr 4;15:1325058. doi: 10.3389/fgene.2024.1325058. eCollection 2024.
Sarcopenia is common in patients with autoimmune diseases (ADs); however, the causal associations between ADs and sarcopenia remain unclear. Therefore, this study investigated the causal associations using bi-directional Mendelian randomization analysis.
Exposure-related single-nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWASs). GWAS statistics for common ADs [Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PSO), and multiple sclerosis (MS)] and sarcopenia-related traits [hand grip strength (HGS), appendicular fat-free mass (FFM), and walking pace] were obtained from public datasets. Inverse-variance weighting as the main method was used to evaluate the causal effect.
Genetically predicted CD had causal effects on whole-body FFM (β = -0.005, = 0.001), leg FFM (β = -0.006, = 1.8E-4; β = -0.007, = 2.0E-4), and arm FFM (β = -0.005, = 0.005; β = -0.005, = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (β = -2.06, = 2.8E-38; β = -2.311, = 2E-20), whole-body FFM (β = -0.842, = 4.7E-10), leg FFM (β = -0.666, = 2.6E-6; β = -0.073, = 2.1E-3), arm FFM (β = -0.63, = 4.4E-6; β = -0.736, = 4.4E-8), and walking pace (β = -1.019, = 6.2E-14). In the reverse direction, HGS (odds ratio [OR] = 10.257, = 3.6E-5; OR = 16.445, = 3.7E-7) had causal effects on CD, while HGS (OR = 0.994, = 0.004; OR = 0.993, = 1.4E-4), leg FFM (OR = 1.003, = 0.005; OR = 1.005, = 1.9E-4), and walking pace (OR = 0.985, = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits.
Our study demonstrated that the genetic susceptibility to CD and RA was associated with high risk of sarcopenia, and some sarcopenia-related traits had causal effects on CD or RA.
肌肉减少症在自身免疫性疾病（ADs）患者中很常见；然而，ADs与肌肉减少症之间的因果关系仍不清楚。因此，本研究使用双向孟德尔随机化分析来研究因果关系。
从全基因组关联研究（GWASs）中提取与暴露相关的单核苷酸多态性（SNPs）。常见ADs（克罗恩病（CD）、溃疡性结肠炎（UC）、类风湿关节炎（RA）、系统性红斑狼疮（SLE）、银屑病（PSO）和多发性硬化症（MS））和肌肉减少症相关特征（握力（HGS）、四肢去脂体重（FFM）和步行速度）的GWAS统计数据来自公共数据集。以逆方差加权法作为主要方法来评估因果效应。
基因预测的CD对全身FFM（β = -0.005，P = 0.001）、腿部FFM（β = -0.006，P = 1.8E - 4；β = -0.007，P = 2.0E - 4）和手臂FFM（β = -0.005，P = 0.005；β = -0.005，P = 0.001）有因果效应，而RA对8个与肌肉减少症相关的特征有因果效应，即HGS（β = -2.06，P = 2.8E - 38；β = -2.311，P = 2E - 20）、全身FFM（β = -0.842，P = 4.7E - 10）、腿部FFM（β = -0.666，P = 2.6E - 6；β = -0.073，P = 2.1E - 3）、手臂FFM（β = -0.63，P = 4.4E - 6；β = -0.736，P = 4.4E - 8）和步行速度（β = -1.019，P = 6.2E - 14）。在反向分析中，HGS（比值比[OR] = 10.257，P = 3.6E - 5；OR = 16.445，P = 3.7E - 7）对CD有因果效应，而HGS（OR = 0.994，P = 0.004；OR = 0.993，P = 1.4E - 4）、腿部FFM（OR = 1.003，P = 0.005；OR = 1.005，P = 1.9E - 4）和步行速度（OR = 0.985，P = 5.7E - 5）与RA存在因果关联。没有证据表明UC、SLE、PSO或MS与肌肉减少症相关特征存在因果关联。
我们的研究表明，CD和RA的遗传易感性与肌肉减少症的高风险相关，并且一些与肌肉减少症相关的特征对CD或RA有因果效应。
