The potential causal association of systemic lupus erythematosus with congestive heart failure in the East Asian population: A two-sample Mendelian randomization study

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that increases the risk of cardiovascular disease, but the causal relationship has remained unknown in the East Asian population. We aim to determine the causal relationship between SLE and congestive heart failure (CHF) in the East Asian population. Methods: We conducted a two-sample Mendelian randomization (MR) study to examine the potential causal association of SLE with CHF, using the East Asian genome-wide association study datasets for SLE (4,222 cases, 8,431 controls) and CHF (9,413 cases, 203,040 controls). Results: The MR analysis showed that genetic susceptibility to SLE was associated with the increased risk of CHF (odds ratio [OR] 1.032, 95% confidence interval [CI] 1.004-1.061, P=0.023). After excluding the human leukocyte antigen (HLA) regions, SLE was also associated with a higher risk of CHF (OR 1.034, 95% CI 1.007-1.062, P=0.015). The multiple MR sensitivity analyses confirmed that this potential causal association was unlikely to be biased by horizontal pleiotropy. Conclusions: The findings of this MR study suggest that SLE potentially increases the risk of CHF in the East Asian population. Genetic predisposition to SLE may play a significant role in developing CHF in the East Asian population.