Genetic Association Between Serum Calcium, Potassium Levels, and Rosacea: Evidence from a Two-Sample Mendelian Randomization Study

YanKun Zhang, Xuan Zhang, Jie Dong, Fang Liu Department of Dermatology, Venereology and Cosmetology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email [email protected]: Recent advances in epidemiological and genetic studies have provided some insights regarding the pathophysiology of rosacea, but the majority of its underlying mechanisms are still poorly understood. In particular, more data are needed to fully understand the role of micronutrients in rosacea development. This study aimed to explore the causality of associations between Calcium, Copper, Selenium, Zinc, Iron, Potassium and Magnesium with the risk of rosacea.Patients and Methods: This was a two-sample Mendelian Randomization (MR) study that used data from genome-wide association studies (GWAS) on serum levels of selected micronutrients as exposure and rosacea as the outcome. The analysis primarily employed the Inverse Variance Weighted (IVW) method. Additional methods included weighted median, weighted mode, and MR-Egger regression. Sensitivity analysis included MR-Egger, MR-PRESSO, Cochran’s Q, and leave-one-out methods. A total of 301 Instrumental Variables were selected for analysis.Results: The genetic prediction indicated a statistically significant association between serum Calcium levels and higher rosacea risk (Odds Ratio (OR) = 2.27, 95% Confidence Interval (CI): 2.02– 2.55, P < 0.001), further confirmed by all supplementary MR methods. Significant association was also found between serum Potassium levels and lower rosacea risk (OR = 0.36, 95% CI: 0.14– 0.93, P = 0.0354), further confirmed by the weighted-median method. Sensitivity analyses showed that the results were robust and not driven by any single factor, with low probability of horizontal pleiotropy.Conclusion: This study found an evidence of a causal association between genetically predicted serum levels of Calcium and Potassium with the risk of rosacea. The roles of these micronutrients should be further studied in rosacea, especially as a link to neurovascular dysregulation and oxidative stress.Keywords: rosacea, micronutrients, Mendelian randomization analysis, calcium, potassium