{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:14:27Z","timestamp":1791465267525,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Polygenic Risk Scores (PRS) are an emerging tool for predicting an individual\u2019s genetic risk to a complex trait. Several methods have been proposed to construct and calculate these scores. Here, we develop a biologically driven PRS using the UK BioBank cohort through validated protein interactions (PPI) and network construction for psoriasis, incorporating variants mapped to the interacting genes of 14 psoriasis susceptibility (PSORS) loci, as identified from previous genetic linkage studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We constructed the PPI network via the implementation of two major meta-databases of protein interactions, and identified variants mapped to the identified PSORS-interacting genes. We selected only European unrelated participants including individuals with psoriasis and randomly selected healthy controls using an at least 1:4 ratio to maximize statistical power. We next compared our PPI-PRS model to (i) clinical risk models and (ii) conventional PRS calculations through <jats:italic>p<\/jats:italic>-value thresholding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our PPI-PRS model provides comparable results to both clinical risk models and conventional approaches, despite the incorporation of a limited number of variants which have not necessarily reached genome-wide significance (GWS). Exclusion of variants mapped to the <jats:italic>HLA-C<\/jats:italic> locus, an established risk locus for psoriasis resulted in highly similar associations compared to our primary model, indicating the contribution of the genetic variability mapped to non-GWS variants in PRS computations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings support the implementation of biologically driven approaches in PRS calculations in psoriasis, highlighting their potential clinical utility in risk assessment and treatment management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2024.1451679","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T06:12:16Z","timestamp":1730873536000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["A polygenic risk score model for psoriasis based on the protein interactions of psoriasis susceptibility loci"],"prefix":"10.3389","volume":"15","author":[{"given":"Charalabos","family":"Antonatos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Koskeridis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana M.","family":"Ralliou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Evangelou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Grafanaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Georgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos K.","family":"Tsilidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Tzoulaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiannis","family":"Vasilopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"D793","DOI":"10.1093\/nar\/gkn665","article-title":"McKusick's online mendelian inheritance in man (OMIM)","volume":"37","author":"Amberger","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41435-023-00222-x","article-title":"Disentangling the complexity of psoriasis in the post-genome-wide association era","volume":"24","author":"Antonatos","year":"2023","journal-title":"Genes Immun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"115D","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: the universal protein knowledgeable","volume":"32","author":"Apweiler","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-4-2","article-title":"An automated method for finding molecular complexes in large protein interaction networks","volume":"4","author":"Bader","year":"2003","journal-title":"BMC Bioinforma."},{"key":"B5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1093\/bioinformatics\/btv546","article-title":"Approximately independent linkage disequilibrium blocks in human populations","volume":"32","author":"Berisa","year":"2016","journal-title":"Bioinformatics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"D1228","DOI":"10.1093\/nar\/gks1147","article-title":"InnateDB: systems biology of innate immunity and beyond\u2014recent updates and continuing curation","volume":"41","author":"Breuer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.3390\/ijms18122526","article-title":"The genetic basis of psoriasis","volume":"18","author":"Capon","year":"2017","journal-title":"Int. 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