Causal Association Between Multiple Sclerosis and Psoriasis: A Genetic Correlation and Mendelian Randomization Study

Abstract Observational studies found a potential bidirectional positive association between multiple sclerosis and psoriasis, but are susceptible to confounding factors. We examined the directionality of causation using Mendelian randomization and estimated the genetic correlation using the linkage disequilibrium score. we performed Mendelian randomization analysis using large-scale genome-wide association studies datasets from the International Multiple Sclerosis Genetics Consortium (IMSGC, 115,803 individuals of European ancestry) and FINNGEN Consortium (252,323 individuals of European ancestry). We selected several Mendelian randomization methods including Causal Analysis Using Summary Effect (CAUSE), inverse variance-weighted (IVW), and pleiotropy-robust methods. CAUSE and IVW indicated that MS reduces the risk of psoriasis (CAUSE OR = 0.93, p = 0.045; IVW OR = 0.93, p = 2.51×10− 20), or vice versa (CAUSE OR = 0.72, p = 0.001; IVW OR = 0.71, p = 4.80×10− 26). Pleiotropy-robust methods with all p-values < 0.05. The linkage disequilibrium score showed no genetic correlation between psoriasis and MS (rg = − 0.071, P = 0.2852). In summary, we provide genetic evidence that MS reduces the risk of psoriasis, and vice versa.