{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:30:01Z","timestamp":1789615801640,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Psoriasis (PSO) is a chronic, systemic immune\u2010mediated inflammatory disease that has been increasingly recognised as being significantly comorbid with various cardiovascular diseases (CVDs). However, the underlying shared genetic architecture and biological mechanisms connecting these conditions remain largely unclear. This study aimed to systematically evaluate the genetic correlations between PSO and four major CVDs\u2014hypertension, coronary heart disease, coronary atherosclerosis, and heart failure\u2014and to identify shared genetic loci, functional genes, and immune\u2010mediated pathways that may serve as potential targets for comorbidity intervention. We integrated multiple large\u2010scale publicly available genome\u2010wide association study datasets and employed a multidimensional genetic analysis framework. This included linkage disequilibrium score regression (LDSC), high\u2010definition likelihood (HDL), stratified LDSC (S\u2010LDSC), multi\u2010dimensional gene\u2010set enrichment (MAGMA), pleiotropy analysis under the composite null hypothesis (PLACO), and summary\u2010data\u2010based Mendelian randomisation (SMR). These approaches were used to elucidate the shared genetic architecture and to functionally annotate the biological mechanisms underlying PSO\u2013CVD comorbidity. LDSC and HDL analyses revealed significant positive genetic correlations between PSO and all four CVDs (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). PLACO identified a total of 653 pleiotropic SNPs, enriched in key genomic loci such as 12q24.12 (e.g., SH2B3, BRAP) and 5q31.1 (e.g., IL3, C5orf56). S\u2010LDSC results demonstrated significant enrichment of these shared signals in disease\u2010relevant tissues including the aorta, coronary arteries, peripheral blood, and spleen. Immune colocalization analysis further highlighted the involvement of T cells, monocytes\/macrophages, and NK cells in the genetic comorbidity between PSO and CVDs. Integrative analyses combining MAGMA, SMR, and FUMA identified multiple potential therapeutic targets, such as APOE, IL13, and C5orf56, that may play key roles in the pathogenesis of both diseases. This study provides the first comprehensive genetic dissection of the comorbidity between PSO and CVDs. We propose a \u201cgenetics\u2013immunity\u2013tissue\u201d regulatory model underlying the shared pathophysiology. Our findings provide potential evidence that PSO, as a systemic condition, may influence cardiovascular pathophysiology.<\/jats:p>","DOI":"10.1111\/exd.70158","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T10:51:18Z","timestamp":1756291878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Comorbidity of Psoriasis and Four Cardiovascular Diseases: Uncovering Shared Mechanisms and Potential Therapeutic Targets"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9131-4659","authenticated-orcid":false,"given":"Xiaojian","family":"Li","sequence":"first","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangren","family":"Yan","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang 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