Mendelian randomization reveals causal effect of Hashimoto's thyroiditis on immune thrombocytopenic purpura

Patients with immune thrombocytopenic purpura (ITP) usually express thyroid antigen-specific antibodies. The purpose of this study was to explore the causal relationship between Hashimoto's thyroiditis (HT) and ITP. A two-sample Mendelian randomization (TSMR) analysis was applied to investigate the potential causal relationship between HT and ITP in European population. Five complementary methods including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode were performed in our study. Risk genes of HT and ITP were selected through Mendelian randomization (MR), and the common risk genes were further analysed by bioinformatics methods to explore the common pathogenesis of the two diseases. The MR analysis revealed a potential causal relationship between HT and risk of ITP [odds ratio (OR) = 1.22; 95% confidence interval (CI) 1.01, 1.49; <i>P</i> = 0.046]. Gene eQTL data were obtained from the IEU database. HT and ITP were respectively treated as outcome variables for MR analysis, and a total of 32 common risk genes were selected, including 12 high-risk genes and 20 low-risk genes. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that risk genes were closely related to antigen processing and presentation, and played a crucial role in the process of various viral and bacterial infections. Our study demonstrated that HT may increase the risk of ITP, and revealed the role of their common risk genes in the development of the two diseases.

免疫性血小板减少性紫癜（immune thrombocytopenic purpura, ITP）患者通常可检测到甲状腺抗原特异性抗体的表达。本研究旨在探究桥本甲状腺炎（Hashimoto's thyroiditis, HT）与ITP之间的因果关联。本研究采用两样本孟德尔随机化（two-sample Mendelian randomization, TSMR）分析方法，针对欧洲人群探究HT与ITP之间的潜在因果关联。本研究共使用5种互补性分析手段，包括逆方差加权（inverse variance weighted, IVW）、孟德尔随机化-Egger（Mendelian Randomization-Egger, MR-Egger）、加权中位数法以及加权众数法。本研究通过孟德尔随机化（Mendelian randomization, MR）筛选HT与ITP的风险基因，并进一步采用生物信息学方法对二者的共同风险基因进行分析，以探究两种疾病的共同发病机制。孟德尔随机化分析结果显示，HT与ITP发病风险存在潜在因果关联[比值比（odds ratio, OR）=1.22；95%置信区间（confidence interval, CI）为1.01~1.49；P=0.046]。基因表达数量性状位点（expression quantitative trait locus, eQTL）数据来源于IEU数据库。本研究分别以HT与ITP作为孟德尔随机化分析的结局变量，最终筛选得到32个共同风险基因，其中包括12个高风险基因与20个低风险基因。包括基因本体论（Gene Ontology, GO）富集分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析在内的功能分析结果显示，上述风险基因与抗原加工提呈过程密切相关，且在多种病毒与细菌感染进程中发挥关键作用。本研究证实HT可升高ITP的发病风险，并揭示了二者共同风险基因在两种疾病发生发展过程中的重要作用。