Mapping the Causal Landscape of Psoriasis: A Systematic Mendelian Randomization Evidence Synthesis and Development of...

Psoriasis is a complex immune-mediated disease closely linked to multiple systemic comorbidities. Although Mendelian randomization (MR) studies have been widely applied to investigate its potential risk factors, existing evidence remains fragmented and sometimes contradictory, limiting clinical translation. This study aimed to systematically consolidate MR findings on psoriasis and to develop an interactive online platform to support clinical decision-making. We systematically searched PubMed, Embase, and Web of Science for psoriasis-related MR studies published up to December 31, 2025, and performed a structured organization and evidence synthesis of the eligible studies. We also developed the MR-PsO Atlas platform using R and Shiny, integrating evidence retrieval, comparative analysis, and exploratory meta-integration where basic comparability was met. A total of 346 MR articles were included, from which 1046 causal associations were extracted. Overall, the findings support an association between disrupted lipid metabolism-particularly elevated LDL-C and certain phospholipid species-and increased psoriasis risk. The results also suggest possible causal links between psoriasis and psychiatric conditions such as depression, and identify IFNLR1 and APOF as potential novel therapeutic targets. For controversial findings, including those related to blood lipids and cancer risk, we further evaluated directional consistency across studies through exploratory meta-integration and discussion of heterogeneity. In addition, the MR-PsO Atlas platform has been successfully deployed and is openly accessible for the retrieval, comparison, and visualization of causal evidence. This study systematically collated published MR evidence on psoriasis and constructed a corresponding evidence atlas to support the retrieval, comparison and interpretation of causal findings. The results highlight multidimensional pathogenic mechanisms ranging from metabolism to immunity. The MR-PsO Atlas platform provides a practical tool for integrating genetic evidence with clinical practice and may help advance precision prevention and management of psoriasis.