{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:31:50Z","timestamp":1790602310475,"version":"4.1.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":43,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Psoriasis is a common inflammatory skin disease with heterogeneous presentation. Up to 30% of individuals have severe disease with a greater surface area of skin involvement, co-morbidity burden and impact on quality of life. Prognostic biomarkers of psoriasis severity could improve allocation of clinical resources and enable earlier intervention to prevent disease progression, and a genetic biomarker would be cost-effective, stable over time, and unaffected by treatment or comorbidity.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Psoriasis severity was studied in four European population-based biobanks (Estonian Biobank, HUNT, FinnGen, UK Biobank) and classified based on level of clinical intervention received, with criteria for severe disease including hospitalisation due to psoriasis, use of systemic immunomodulating therapy or phototherapy. Common genetic variants, polygenic risk scores and traditional epidemiological risk factors were tested for association with severe psoriasis in each of the constituent biobanks and combined through meta-analysis. The distribution of psoriasis polygenic risk was also evaluated in a cohort of 4151 participants in the UK-based severe psoriasis registry, BSTOP, and a cohort of 1461 participants from Novartis clinical trials of secukinumab for psoriasis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the population-based datasets, 9738 of 44,904 individuals with psoriasis (21.7%) were classified as having severe disease. Genetic variants within the major histocompatibility complex (MHC) and the\n TNIP1<\/jats:italic>\n and\n IL12B<\/jats:italic>\n psoriasis susceptibility loci were associated with severe disease at genome-wide significance (\n P<\/jats:italic>\n \u2009<\u20095.0\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n ). Furthermore, a strong positive correlation was observed between psoriasis susceptibility and severity effect sizes across all psoriasis susceptibility loci. An individual\u2019s genetic liability to psoriasis as measured with a polygenic risk score (PRS) strongly associated with disease severity, with a magnitude of effect comparable to established severity risk factors such as obesity and smoking. The top 5% of psoriasis cases by genetic liability to psoriasis were 1.23-to-2.00 times as likely than the average psoriasis case to have severe disease. Psoriasis cases in our external validation datasets (BSTOP registry and Novartis clinical trials) were enriched for a PRS that exceeded the 95th percentile established among UK Biobank psoriasis cases by 3.06-fold and 2.32-fold respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The psoriasis susceptibility PRS demonstrates utility and may be more effective than established epidemiological factors, as a stratification tool to identify those individuals that are at greatest risk of severe disease and may benefit most from early intervention.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s13073-025-01561-2","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:27:04Z","timestamp":1765960024000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic liability to psoriasis predicts severe disease 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Information about ethics oversight in the UK Biobank can be found at\n \n .BSTOP is an ongoing prospective observational study of patients with moderate\u2012severe plaque psoriasis across\u2009>\u200970 UK dermatology centres, which includes biological sample collection. Participants were adults (aged\u2009>\u200916\u00a0years) at the time of recruitment; and provided written informed consent (BSTOP received approval from the London \u2013 Westminster Research Ethics Committee [previously called South East London REC 2 when originally approved in 2011], reference 11\/H0802\/7).The Novartis data was a post hoc analysis of existing anonymized clinical trial data collected by Novartis Pharmaceuticals. All trials included in the study are listed in Additional File 2: Supplementary Methods, which includes NCT numbers to allow further information to be found via clinicaltrials.gov. The site investigators collected the data and Novartis Pharmaceuticals conducted the data analyses. The studies were approved by the institutional review board or ethics committee at each participating site, and the studies were conducted in accordance with the ethical principles of the Declaration of Helsinki. U.S. sites maintained compliance with Health Insurance Portability and Accountability Act regulations. Eligible patients provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CHS is an investigator on EC-IMI funded consortia with multiple industry partners (see HIPPOCRATES-IMI.eu and BIOMAP-IMI.eu); departmental research funding from Sanger as part of Open Targets programme, Astrazeneca, Boehringer Ingelheim. SJB has received research funding (but no personal financial benefits) from the Wellcome Trust (senior research fellowship ref 220875\/Z\/20\/Z), UKRI, Medical Research Council, Rosetrees Trust, Stoneygates Trust, British Skin Foundation, Charles Wolfson Charitable Trust, anonymous donations from people with eczema, Unilever, Pfizer, Abbvie, Sosei-Heptares, Janssen, European Lead Factory (multiple industry partners) and the BIOMAP consortium (EC-IMI project ref 821511). SL, CC, SK, EdR (affiliated to Target, Disease & Systems Biology, Sanofi Research, Cambridge, MA, USA) and KK (affiliated to Genetics Research, Sanofi, Cambridge, MA, USA) are Sanofi employees and may hold shares and\/or stock options in the company. SKM reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sanofi, and UCB, outside the submitted work. DDG has received grants and\/or consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JZ, SB, FK (all authors affiliated to Immunology Disease Area, Biomedical Research, Novartis Pharma AG, Basel, Switzerland) are employees and shareholders of Novartis Pharma AG. The remaining authors declare that they have no competing interests. These include those affiliated to Newlab Clinical Research Inc, St. John\u2019s, NL, Canada,","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}