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Journal article
Genetic liability to psoriasis predicts severe disease outcomes
Genome medicine, In Press
2025
PMID: 41408349
Abstract
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.
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.
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 TNIP1 and IL12B psoriasis susceptibility loci were associated with severe disease at genome-wide significance (P < 5.0 × 10
). Furthermore, a strong positive correlation was observed between psoriasis susceptibility and severity effect sizes across all psoriasis susceptibility loci. An individual's 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.
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.
Details
- Title
- Genetic liability to psoriasis predicts severe disease outcomes
- Authors/Creators
- Jake R Saklatvala - King's College LondonSamuel Lessard - SanofiMaris Teder-Laving - University of TartuLaurent F Thomas - Norwegian University of Science and TechnologyRavi Ramessur - King's College LondonJonas Zierer - NovartisBjørn Olav Åsvold - Norwegian University of Science and TechnologyAnne Barton - Versus ArthritisDavid Baudry - King's College LondonJohn Bowes - Versus ArthritisBen Brumpton - Norwegian University of Science and TechnologySandro Bruno - NovartisVinod Chandran - Toronto Western HospitalClément Chatelain - SanofiEmanuele de Rinaldis - SanofiJames T Elder - University of MichiganDavid Ellinghaus - Christian-Albrechts-Universität zu KielJohn Foerster - University of DundeeAndre Franke - Christian-Albrechts-Universität zu KielDafna D Gladman - University Health NetworkWayne Gulliver - Memorial University of NewfoundlandUlrike Hüffmeier - Universitätsklinikum ErlangenLaura Huilaja - Oulu University HospitalKristian Hveem - Norwegian University of Science and TechnologyShameer Khader - Target, Disease & Systems Biology, Sanofi Research, Cambridge, MA, USAKülli Kingo - University of TartuKatherine Klinger - SanofiFrank Kolbinger - NovartisSulev Kõks - Murdoch UniversityWilson Liao - University of California, San FranciscoRajan P Nair - University of MichiganJoanne Nititham - University of California, San FranciscoProton Rahman - Memorial University of NewfoundlandAndré Reis - Universitätsklinikum ErlangenManpreet K Sagoo - King's College LondonPhilip E Stuart - University of MichiganKaisa Tasanen - Oulu University HospitalTanel Traks - University of TartuLam C Tsoi - University of MichiganSteffen Uebe - Universitätsklinikum ErlangenKatie Watts - University of BristolJonathan N Barker - King's College LondonSatveer K Mahil - King's College LondonSinéad M Langan - FacultySara J Brown - NHS LothianMari Løset - Department of Dermatology, Clinic of Orthopedy, Rheumatology and Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, NorwayLavinia Paternoster - MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UKNick Dand - King's College LondonCatherine H Smith - King's College LondonMichael A Simpson - King's College LondonBSTOP study group
- Publication Details
- Genome medicine, In Press
- Publisher
- Springer Nature
- Grant note
- NIHR302258 / NIHR Advanced Fellowship MC_UU_00011/1, MC_UU_00032/01 / UK Medical Research Council Integrative Epidemiology Unit 220875/Z/20/Z / Wellcome Trust PRG1911 and TK (TK214) / Estonian Research Council 821511 / Innovative Medicines Initiative 2 Joint Undertaking
- Identifiers
- 991005840054207891
- Copyright
- © The Author(s) 2025.
- Murdoch Affiliation
- Personalised Medicine Centre
- Language
- English
- Resource Type
- Journal article
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