以全基因组关联分析大数据为基础的孟德尔随机化方法探究类风湿性关节炎与宫颈癌发病风险的因果关联

Mendelian Randomization Based on Big-Genome Association Analysis to Explore Causal Associations Between Rheumatoid Arthritis and Risk of Cervical Cancer

目的通过孟德尔随机化(Mendelian randomization,MR)方法,探究类风湿性关节炎(rheumatoid arthritis,RA)与宫颈癌发病风险的因果关联。方法以全基因组关联分析研究(Genome Wide Association Study,GWAS)数据为基础,筛选出与RA的关联有单核苷酸多态性(single nucleotide polymorphism,SNP)作为基因工具变量,利用逆方差加权分析方法(inverse variance weighted analysis,IVW)、加权中值方法和MR⁃Egger方法三种孟德尔随机化方法探究类风湿性关节炎与宫颈癌发病风险的因果关联。分析结果以比值比(odds ratio,OR)和95%可信区间(confidence interval,CI)显示,以P<0.05为效应具有统计学意义。结果共筛选到8个与RA相关的SNP。IVW结果显示,RA是宫颈癌发病风险的危险因素(OR=1.14,95%CI 1.10~1.18,P<0.001);加权中值法和MR⁃Egger效应估计值具有相似的统计结果。敏感性分析发现没有对因果估计结果产生较大的SNP。结论RA是宫颈癌发病风险的危险因素,加强RA患者宫颈癌的筛查、预防,对于降低该人群的宫颈癌发病率具有重要意义。

Objective To explore the causal relationship between rheumatoid arthritis(RA)and the risk of cervical cancer by Mendelian randomization(MR).Methods Based on Genome Wide Association Study(GWAS)data,single nucleotide polymorphism(SNP)associated with RA were selected as genetic instrumental variables.Three Mendelian randomization methods,inverse variance weighted analysis(IVW),weighted median methods and MR-Egger were used to investigate the causal association between RA and the risk of cervical cancer.The analysis results were shown by odds ratio(OR)and 95%confidence interval(CI),and the effect was statistically significant with P<0.05.Results Eight SNPs related to RA were included.The result of IVW show that RA was a risk factor for the risk of cervical cancer(OR=1.14,95%CI 1.10~1.18,P<0.001).Weighted median method and MR-Egger provided the similar result.Sensitivity analysis found that no single SNP was strongly orreversely driving the overall effect for causal estimates.Conclusions RA was a risk factor of cervical cancer.Strengthening the screening and prevention of cervical cancer in RA patients was of great significance to reduce the incidence of cervical cancer in this population.