| Title: | Polygenic prediction of actinic keratosis identifies transplant recipients at risk of extreme lesion burden |
| Journal: | American Journal of Transplantation |
| Published: | 13 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42595125/ |
| DOI: | https://doi.org/10.1016/j.ajt.2026.08.006 |
Publication 21020
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Abstract
Transplant recipients have an elevated risk of actinic keratosis (AK), a precursor for squamous cell carcinoma (SCC). We assessed whether an AK polygenic risk score (PRS) can identify transplant-naive individuals and transplant recipients at risk of multiple AKs who may benefit from early prevention. Using genome-wide association data (140,339 cases; 1,430,776 controls), we developed an AK PRS and evaluated it in cohort studies of European descent individuals in QSkin (N=12,843), STAR (N=357), UK Biobank (N=963), and All of Us (N=1,859). The PRS was strongly associated with high AK burden in transplant-naive individuals, conferring a five-fold increased risk of developing ≥20 AKs (OR per standard deviation (SD) increase in the PRS =5.06, 95%CI=4.69-5.46). In transplant recipients, it was associated with up to a 2.5-fold increased risk of developing ≥1 AK (UKB OR per SD =2.49, 95%CI=1.91-3.23; STAR OR per SD=1.79, 95%CI=1.10-2.91; All of Us OR per SD=1.52, 95%CI=1.35-1.70). The PRS improved prediction of ≥20 AKs by 13% beyond age and sex (AUC 0.90 vs 0.77) and identified the highest-risk 20% with a 9-fold increased risk in transplant-naive individuals (OR=8.61, 95%CI=7.26-10.22) and a 2-fold increased risk in transplant recipients (OR=2.23, 95%CI=1.26-4.20), compared to the middle-risk 60%. Incorporating PRS into pre- and post-transplant care could enable earlier, personalised prevention.</p>
8 Authors
- Abishna Parasuraman
- Rawaa Eltayib
- Nirmala Pandeya
- Catherine M Olsen
- Matthew H Law
- David C Whiteman
- Stuart MacGregor
- Mathias Seviiri
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
Enabling scientific discoveries that improve human health