Causal relationship between several autoimmune diseases and renal malignancies: A two-sample mendelian randomization study.

OBJECTIVE: Observational studies have shown an association between systemic autoimmune disease (AD) and multiple malignancies. However, due to the difficulty indetermining the temporal nature of the order, their causal relationship remains elusive. Based on pooled data from a large population-wide genome-wide association study (GWAS), this study explores the genetic causality between systemic autoimmune disease and renal malignancy.

METHODS: We took a series of quality control steps from a large-scale genome-wide association study to select single nucleotide polymorphisms (SNPs) associated with systemic autoimmune disease as instrumental variables(IVs) to analyze genetic causality with renal malignancies. Inverse variance weighting (IVW), MR- Egger, weighted median, simple model and weighted model were used for analysis. The results were mainly based on IVW (Random Effects), followed by sensitivity analysis. Inverse-Variance Weighted(IVW) and MR-Egger were used to test for heterogeneity. MR- Egger is also used for pleiotropic testing. A single SNP analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate causality, and sensitivity analysis was performed to evaluate pleiotropy and instrumental validity.

RESULTS: Acute and subacute iridocylitis (P = 0.006, OR = 1.077), Ankylosing spondylitis (P = 0.002, OR = 1.051), and spondyloarthritis (P = 0.009, OR = 1.073) were positively associated with an increased risk of renal malignancy. Coxarthrosis (P = 0.008, OR = 0.483), Juvenile rheumatism (P = 0.011, OR = 0.897), and Systemic lupus erythematosus (P = 0.014, OR = 0.869) were negatively associated with an increased risk of renal malignancy. The results of sensitivity analysis were consistent without heterogeneity or pleiotropy.

CONCLUSION: Our study suggests a causal relationship between different systemic autoimmune diseases and renal malignancies. These findings prompt health care providers to take seriously the potential risk of systemic autoimmune disease and provide new insights into the genetics of kidney malignancies.