Study on causal relationship between rheumatoid arthritis and pulmonary hypertension based on Mendelian randomization
Objective To investigate the causal relationship between rheumatoid arthritis (RA) and pulmonary hypertension (PH) by the Mendelian randomization design method.Methods The data on single nucleotide polymorphisms (SNPs) of exposure and outcome were obtained by using publicly available ge-nome-wide association studies and the summary analysis was conducted;the inverse variance-weighted (IVW) method as the primary analysis method was used to assess the causal effect of exposure factors (RA) on the outcomes (PH);the MR-Egger regression method,weighted median method (WM),weighted model and sim-ple model were used as supplementary regression explanations to conduct the sensitivity analysis for evalua-ting the robustness of results;the "heterogeneity" function was used to calculate the "P value" for testing the heterogeneity,and the "horizontal pleiotropy" function was used to calculate the "P value" to test the level pleiotropy.Results In the "FINNGEN data" included in the GWAS database,the SNPs had the strong corre-lation after removing the linkage imbalance by Mendelian random analysis and satisfying "P<5×10-8" were selected,the effective instrumental variables were obtained by integrating the exposure and outcome.The IVW results showed that RA was a risk factor for PH (OR=1.295,95%CI:1.053-1.593,P=0.014)."heteroge-neity" function test showed that the results had no heterogeneity (P=0.221);" horizontal pleiotropy" func-tion test showed that the results had no horizontal pleiotropy (P=0.877),and the total results were steady and reliable.Conclusion RA is a risk factor for PH,and RA is positively associated with PH.
rheumatoid arthritispulmonary hypertensionMendelian randomization analysiscausal association