Associations and mediators between vitiligo and cardiovascular diseases: a Mendelian randomization study

Abstract

Abstract Previous studies yielded conflicting results on the associations between vitiligo and cardiovascular diseases (CVD), and its underlying mechanisms remain unclear. This MR study aims to elucidate the underlying causal association between vitiligo and the risk of CVD, as well as the potential mediator. Using summary statistics from genome-wide association study (GWAS), we conducted a bidirectional two-sample Mendelian randomization (MR) analysis and mediation analysis to investigate the causal association between vitiligo and 13 CVD outcomes and potential mediators. The IVW method was the main MR analysis method, supplemented by MR-Egger, weighted median, and weighted mode methods. Multiple sensitivity analyses were applied to enhance the robustness of the results. Bioinformatics analysis involved Protein-Protein Interaction (PPI) network, Gene Ontology (GO) and GeneMANIA functional analysis analysis. MR analysis indicated that genetically predicted vitiligo was significantly associated with higher risk of coronary heart disease (CHD) (OR = 1.0199, 95% CI = 1.0024–1.0377, p = 0.026). There was no significant causal association between vitiligo and 12 other cardiovascular diseases. And reverse MR analysis found no causal effect of CVD on vitiligo. CCL11 was identified to partially mediate the association between vitiligo and CHD. GO and GeneMANIA suggested that CCL11 may mediate the association between vitiligo and CHD through chemokine-related functions and pathways. Our study revealed the potential causal association between vitiligo and CHD, with CCL11 as a potential mediator. Further studies are necessitated to elucidate the exact association and the mechanisms.