| Title: |
Genetic liability to psoriasis predicts severe disease outcomes. |
| Authors: |
Saklatvala, Jake R; Lessard, Samuel; Teder-Laving, Maris; Thomas, Laurent F; Ramessur, Ravi; Zierer, Jonas; Åsvold, Bjørn Olav; Barton, Anne; Baudry, David; Bowes, John; Brumpton, Ben; Bruno, Sandro; Chandran, Vinod; Chatelain, Clément; de Rinaldis, Emanuele; Elder, James T; Ellinghaus, David; Foerster, John; Franke, Andre; Gladman, Dafna D; Gulliver, Wayne; Hüffmeier, Ulrike; Huilaja, Laura; Hveem, Kristian; Khader, Shameer; Kingo, Külli; Klinger, Katherine; Kolbinger, Frank; Kõks, Sulev; Liao, Wilson; Nair, Rajan P; Nititham, Joanne; Rahman, Proton; Reis, André; Sagoo, Manpreet K; Stuart, Philip E; Tasanen, Kaisa; Traks, Tanel; Tsoi, Lam C; Uebe, Steffen; Watts, Katie; BSTOP study group; Barker, Jonathan N; Mahil, Satveer K; Langan, Sinéad M; FinnGen; Estonian Biobank research team; Brown, Sara J; Løset, Mari; Paternoster, Lavinia; Dand, Nick; Smith, Catherine H; Simpson, Michael A |
| Publisher Information: |
BMC |
| Publication Year: |
2025 |
| Collection: |
London School of Hygiene & Tropical Medicine: LSHTM Research Online |
| Description: |
BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 10-8). 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
1756-994X |
| Relation: |
https://researchonline.lshtm.ac.uk/id/eprint/4680173/1/Saklatvala-etal-2026-Genetic-liability-to-psoriasas.pdf; Saklatvala, Jake R; Lessard, Samuel; Teder-Laving, Maris; Thomas, Laurent F; Ramessur, Ravi; Zierer, Jonas; Åsvold, Bjørn Olav; Barton, Anne; Baudry, David; Bowes, John; +43 more.Brumpton, Ben; Bruno, Sandro; Chandran, Vinod; Chatelain, Clément; de Rinaldis, Emanuele; Elder, James T; Ellinghaus, David; Foerster, John; Franke, Andre; Gladman, Dafna D; Gulliver, Wayne; Hüffmeier, Ulrike; Huilaja, Laura; Hveem, Kristian; Khader, Shameer; Kingo, Külli; Klinger, Katherine; Kolbinger, Frank; Kõks, Sulev; Liao, Wilson; Nair, Rajan P; Nititham, Joanne; Rahman, Proton; Reis, André; Sagoo, Manpreet K; Stuart, Philip E; Tasanen, Kaisa; Traks, Tanel; Tsoi, Lam C; Uebe, Steffen; Watts, Katie; BSTOP study group; Barker, Jonathan N; Mahil, Satveer K; Langan, Sinéad M ORCID logo; FinnGen; Estonian Biobank research team; Brown, Sara J; Løset, Mari; Paternoster, Lavinia; Dand, Nick; Smith, Catherine H; and Simpson, Michael A (2025) Genetic liability to psoriasis predicts severe disease outcomes. Genome medicine, 18 (1). p. 14. ISSN 1756-994X DOI:10.1186/s13073-025-01561-2 |
| Availability: |
https://researchonline.lshtm.ac.uk/id/eprint/4680173/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.1C17892F |
| Database: |
BASE |