Background: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.Methods: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.Results:Genetically predicted CD had causal effects on whole-body FFM (β = −0.005, p = 0.001), leg FFM (βleft = −0.006, p = 1.8E-4; βright = −0.007, p = 2.0E-4), and arm FFM (βleft = −0.005, p = 0.005; βright = −0.005, p = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (βleft = −2.06, p = 2.8E-38; βright = −2.311, p = 2E-20), whole-body FFM (β = −0.842, p = 4.7E-10), leg FFM (βleft = −0.666, p = 2.6E-6; βright = −0.073, p = 2.1E-3), arm FFM (βleft = −0.63, p = 4.4E-6; βright = −0.736, p = 4.4E-8), and walking pace (β = −1.019, p = 6.2E-14). In the reverse direction, HGS (odds ratio [OR]left = 10.257, p = 3.6E-5; ORright = 16.445, p = 3.7E-7) had causal effects on CD, while HGS (ORleft = 0.994, p = 0.004; ORright = 0.993, p = 1.4E-4), leg FFM (ORleft = 1.003, p = 0.005; ORright = 1.005, p = 1.9E-4), and walking pace (OR = 0.985, p = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits.Conclusion: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.

中文翻译：

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自身免疫性疾病与肌肉减少症相关特征之间的因果关系：双向孟德尔随机化研究

背景：肌肉减少症在自身免疫性疾病（AD）患者中很常见；然而，AD 与肌肉减少症之间的因果关系仍不清楚。因此，本研究采用双向孟德尔随机化分析来调查因果关系。方法：从全基因组关联研究（GWAS）中提取与暴露相关的单核苷酸多态性（SNP）。常见 AD [克罗恩病 (CD)、溃疡性结肠炎 (UC)、类风湿性关节炎 (RA)、系统性红斑狼疮 (SLE)、银屑病 (PSO) 和多发性硬化症 (MS)] 和肌少症相关特征的 GWAS 统计数据 [手]握力（HGS）、四肢去脂质量（FFM）和步行速度]从公共数据集中获得。以逆方差加权为主要方法来评估因果效应。结果：基因预测的CD对全身FFM（β = -0.005，p = 0.001）、腿部FFM（βleft = -0.006，p = 1.8E-4；βright = -0.007，p = 2.0E-4）和手臂 FFM（βleft = -0.005，p = 0.005；βright = -0.005，p = 0.001），而 RA 对 8 种肌少症有因果影响-相关性状，即 HGS（βleft = −2.06，p = 2.8E-38；βright = −2.311，p = 2E-20）、全身 FFM（β = −0.842，p = 4.7E-10）、腿部FFM（βleft = -0.666，p = 2.6E-6；βright = -0.073，p = 2.1E-3），臂 FFM（βleft = -0.63，p = 4.4E-6；βright = -0.736，p = 4.4 E-8) 和步行速度 (β = -1.019, p = 6.2E-14)。相反，HGS（比值比 [OR]left = 10.257，p = 3.6E-5；ORright = 16.445，p = 3.7E-7）对 CD 具有因果影响，而 HGS（ORleft = 0.994，p = 0.004） ；ORright = 0.993，p = 1.4E-4)、腿部 FFM (ORleft = 1.003，p = 0.005；ORright = 1.005，p = 1.9E-4) 和步行速度 (OR = 0.985，p = 5.7E-5) ）与 RA 有因果关系。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系。结论：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，并且一些肌肉减少症相关特征具有因果关系在 CD 或 RA 上。