Genetic Association of Lipids and Lipid‐Lowering Drug Target Genes With Atopic Dermatitis: A Drug Target Mendelian Randomization Study

Background and Aims Several observational studies have reported inconsistent associations between dyslipidaemia, stains use and atopic dermatitis (AD). Nevertheless, the available data on the effects of –C‐lowering as well as TG‐lowering drugs remain inconclusive and limited. The aim of this study was to evaluate the causal association of lipid traits and long‐term use of lipid‐lowering drugs on AD risk. Methods Drug‐targeted Mendelian randomization analyses were performed in European ancestry. Pooled statistics on low‐density lipoprotein cholesterol, triglyceride and AD were extracted from large genome‐wide association studies datasets. Instrumental variables located in and around lipid‐lowering target genes were used as proxies for therapeutic inhibition of these target genes. Inverse‐variance‐weighted approach was applied as the primary analysis. Results We explored the role of seven lipid‐lowering target genes in AD, among which genetically proxied Niemann‐Pick C1–like 1 inhibition, a target of LDL‐C‐lowering drugs, was associated with an increased risk of AD (odds ratio, 3.03; 95% CI, 1.36–6.75; p = 0.007). This association was replicated in FinnGen cohort (odds ratio, 1.72; 95% CI, 1.09–2.72; p = 0.020). A series of sensitivity analyses confirmed the robustness of the estimates. Conclusion We found no genetic support for the repurposing of seven lipid‐lowering drug targets for the prevention of AD. However, pharmacovigilance of AD risk in Niemann‐Pick C1–like 1 inhibitor users may be warranted.