线粒体 DNA 拷贝数与自身免疫性疾病的风险:带有荟萃分析的孟德尔随机研究

IF 4.7 Q2 IMMUNOLOGY
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引用次数: 0

摘要

背景线粒体 DNA 在自身免疫性疾病(ADs)的病理生理学中起着至关重要的作用。然而,线粒体DNA拷贝数(mtDNA-CN)与自身免疫性疾病风险之间的关系却存在争议。本研究使用三组独立的工具变量(IV)进行了孟德尔随机化(MR)分析和荟萃分析,以研究 mtDNA-CN 与 20 种 ADs 之间的潜在关联。使用芬兰基因队列的汇总统计数据调查了AD的结果数据。使用逆方差加权(IVW)、MR-Egger 和加权中位数方法评估了潜在的因果关系。敏感性分析和 Steiger 检验用于验证 MR 估计值的稳健性。结果总体而言,基因预测的 mtDNA-CN 与 ADs 风险无关(OR = 1.046,95 % CI:0.964-1.135,P = 0.283)。然而,亚组分析显示,mtDNA-CN 与自身免疫性甲状腺功能减退症(OR = 1.133,95 % CI:1.016-1.262,P = 0.024)和类风湿性关节炎(OR = 1.219,95 % CI:1.028-1.445,P = 0.023)存在正向因果关系。相比之下,mtDNA-CN 与特应性皮炎、银屑病、溃疡性结肠炎、成人型静止病、1 型糖尿病、克罗恩病、肉样瘤病、强直性脊柱炎、多发性硬化症、自身免疫性关节炎和类风湿性关节炎(OR = 1.219,95 % CI:1.028-1.445,P = 0.023)之间没有因果关系、多发性硬化症、自身免疫性甲状腺功能亢进症、原发性硬化性胆管炎、系统性红斑狼疮、系统性硬化症、斑秃、重症肌无力、格林-巴利综合征、皮肌炎和白癜风。结论这项磁共振分析表明,mtDNA-CN 与自身免疫性甲状腺功能减退症和类风湿性关节炎的遗传风险增加有因果关系。这些发现对于在临床实践中使用 mtDNA-CN 作为自身免疫性甲状腺功能减退症和类风湿性关节炎风险评估的生物标志物具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis

Background

Mitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs.

Methods

The three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups.

Results

Overall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo.

Conclusions

This MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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