Causal effects of fatty acids on type 2 inflammatory skin diseases: Mendelian randomization study

Previous studies have found that fatty acids may be associated with type 2 inflammatory skin diseases, but the potential causal relationship is still difficult to determine. Therefore, the purpose of this study is to use Mendelian randomization to determine whether there is a causal relationship between fatty acid levels and type 2 inflammatory skin disease. We conducted univariate and multivariate Mendelian randomization (MR) analysis using statistical data collected from genome-wide association studies (GWAS), including total fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, Omega-3 unsaturated fatty acids, Omega-6 unsaturated fatty acids, Omega-6 to Omega-3 fatty acid ratio, docosahexaenoic acid (DHA), linoleic acid (LA), atopic dermatitis, urticaria, nodular prurigo, and bullous pemphigus. In this study, inverse variance weighting (IVW) was used as the main analysis method, and weighted median, MR Egger, Simple mode, and weighted mode were selected as auxiliary analyses to enhance the reliability of our results. We used Cochrane Q test and MR Egger intercept test for heterogeneity and horizontal pleiotropy testing, as well as a series of sensitivity analyses to improve the accuracy and stability of our results. We used Bayesian weighted Mendelian randomization (BWMR) to test our MR analysis results. Univariate Mendelian randomization analysis showed that Omega-3 and DHA were negatively correlated with the risk of atopic dermatitis and urticaria, and PUFA was also negatively correlated with the risk of urticaria. On the contrary, omega-6:3 is positively correlated with the onset of atopic dermatitis, urticaria, and prurigo noduraris. The Cochrane Q test and MR Egger intercept test suggest that our experimental results are not affected by heterogeneity and horizontal pleiotropy, and subsequent sensitivity analysis also demonstrates the reliability of our results. Multivariate Mendelian randomization analysis showed a negative correlation between omega-3 levels and the risk of developing urticaria and prurigo nodularis. The BWMR results were consistent with univariate Mendelian randomization analysis, but the effect of DHA on atopic dermatitis lost statistical significance. Conclusion: This study found that Omega-3 (including DHA) has a protective effect on the risk of atopic dermatitis and urticaria, while PUFA also has a protective effect on the risk of urticaria. However, omega-6:3 is a potential risk factor for atopic dermatitis, urticaria, and nodular prurigo, providing a new overview of the impact of fatty acids on type 2 inflammatory skin diseases.