{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:00Z","timestamp":1787028240370,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: The advent of biologics targeting key inflammatory pathways has significantly advanced psoriasis treatment. Among them, the Interleukin-23 inhibitors Guselkumab and Risankizumab have demonstrated high efficacy and rapid clinical response in both clinical trials and real-world studies. However, up to 30% of patients fail to respond. This study aimed to identify pharmacogenetic markers associated with treatment response using a genome-wide association study (GWAS) and protein network-based approach. Methods: Fifty-three patients of Greek origin with moderate-to-severe plaque psoriasis were treated with Guselkumab or Risankizumab. Based on Psoriasis Area and Severity Index (PASI) improvement at 3 and 6 months, patients were categorized as responders or non-responders. Approximately 730,000 single-nucleotide polymorphisms (SNPs) were genotyped. After filtering, a GWAS was performed to identify variants associated with treatment response. Additionally, protein\u2013protein interaction (PPI) network analysis was applied to the two Interleukin-23 subunits and SNPs within or near genes encoding Interleukin-23-interacting proteins to test for their association. Results: The GWAS identified two novel variants, rs73641950 and rs6627462, significantly associated with treatment response, with both surpassing the genome-wide significance threshold after Bonferroni correction. The PPI-based approach revealed rs13086445, located downstream of the Interleukin-12 subunit alpha (IL12A) gene, as another associated variant. All three SNPs lie in genomic regions with potential regulatory roles. Conclusions: This study identifies three novel genetic variants associated with response to Interleukin-23 inhibitors in psoriasis. These findings provide promising pharmacogenetic markers which, upon validation in larger, independent cohorts, will enable the translation of a patient\u2019s genotype into a response phenotype, thereby guiding clinical decisions and improving drug effectiveness.<\/jats:p>","DOI":"10.3390\/genes16101195","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Genome-Wide Association Study Identifying Novel Genetic Markers of Response to Treatment with Interleukin-23 Inhibitors in Psoriasis"],"prefix":"10.3390","volume":"16","author":[{"given":"Sophia","family":"Zachari","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-3394","authenticated-orcid":false,"given":"Kalliopi","family":"Liadaki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Planaki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efterpi","family":"Zafiriou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kouvarou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Gerogianni","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-5432","authenticated-orcid":false,"given":"Themistoklis","family":"Giannoulis","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Thessaly, Gaiopolis, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-8927","authenticated-orcid":false,"given":"Zissis","family":"Mamuris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-7902","authenticated-orcid":false,"given":"Dimitrios P.","family":"Bogdanos","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-537X","authenticated-orcid":false,"given":"Nicholas K.","family":"Moschonas","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26500 Patras, Greece"},{"name":"Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theologia","family":"Sarafidou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yi, R.C., Akbik, M., Smith, L.R., Klionsky, Y., and Feldman, S.R. 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