Causal Effect of Plasma Fatty Acid Profiles on Psoriasis Risk: Genetic Evidence from a Mendelian Randomization Study

Lei Yao,1,* Xi Wang,2,* Dongmei Lu,3 Suyan Tian4 1Department of Dermatology, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2School of Mathematics, Jilin University, Changchun, Jilin, 130012, People’s Republic of China; 3Department of General Education, Changchun College of Electronic Technology, Changchun, Jilin, 130000, People’s Republic of China; 4Division of Clinical Research, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Suyan Tian, Division of Clinical Research, The First Hospital of Jilin University, 1 Xinmin Street, Changchun, Jilin, 130021, People’s Republic of China, Email [email protected] Dongmei Lu, Department of General Education, Changchun College of Electronic Technology, 333 Xueli Road, Changchun, Jilin, 130000, People’s Republic of China, Email [email protected]: Emerging evidence indicates that omega-3 fatty acids from fish oil may serve as beneficial dietary supplements for psoriasis management. Clinical observations demonstrate a significant association between psoriasis improvement and increased docosahexaenoic acid (DHA) levels. However, the causal relationship between fatty acids and psoriasis risk requires further investigation.Methods: Using summary-level genome-wide association study (GWAS) data, we applied univariable (UVMR), reverse, and multivariable (MVMR) Mendelian randomization analyses to assess causal effects of multiple fatty acids—including polyunsaturated (PUFA), saturated (SFA), monounsaturated (MUFA), omega-3/6 fatty acids, DHA, eicosapentaenoate (EPA) and docosapentaenoate (DPA)—on psoriasis risk.Results: The analysis revealed that higher circulating levels of omega-3 fatty acids were significantly associated with a reduced risk of psoriasis development (UVMR: OR = 0.900, p = 0.022; MVMR: OR = 0.862, p = 0.007). Sensitivity analyses supported the robustness of this causal relationship, with consistent effects across multiple MR methods. Notably, DHA (UVMR: OR = 0.788, p = 0.006; MVMR: OR = 0.856, p = 0.021) drove this inverse association, while EPA and DPA showed marginal contributions.Conclusion: This study provides valuable insights for targeted nutritional strategies to prevent and manage psoriasis, but further validation is needed.Keywords: psoriasis, causal inference, fatty acids, Mendelian randomization