Exonic Variation in HLA-C, CFB, and TAP2 Associated With Increased Risk for Comorbid Crohn's Disease and Psoriasis
Vikram R Shaw1, Jinyoung Byun2, Catherine Zhu1
1Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA.
International Journal of Dermatology
|November 19, 2025
Summary
Genetic variants in HLA-C, CFB, and TAP2 are linked to the rare comorbidity of psoriasis (PS) and Crohn
Area of Science:
- Genetics
- Immunology
- Dermatology
- Gastroenterology
Background:
- Psoriasis (PS) and Crohn's disease (CD) are chronic immune-mediated inflammatory conditions with shared underlying mechanisms.
- While rare, a significant association exists between PS and CD, suggesting common genetic influences.
- Understanding the genetic basis of this comorbidity is crucial for personalized medicine.
Purpose of the Study:
- To identify novel genetic variations associated with the comorbidity of psoriasis and Crohn's disease.
- To compare the genetic architecture of comorbid PS/CD with PS or CD alone.
- To validate findings in independent patient cohorts.
Main Methods:
- Focused exome-wide association study (ExWAS) in UK Biobank (UKB) participants.
- Case-control design comparing comorbid PS/CD cases to healthy controls and PS/CD alone cases.
- Validation analysis in the All of Us (AoU) Research Program.
Main Results:
- The genetic profile of comorbid PS/CD resembles that of PS alone.
- Three protein-coding variants in HLA-C, CFB, and TAP2 were significantly associated with comorbidity.
- Combined carriage of these three risk variants showed a strong association with comorbid disease in both UKB and AoU cohorts.
Conclusions:
- Novel exonic, protein-coding genetic variations are associated with PS and CD comorbidity.
- A trigenic risk score involving variants in HLA-C, CFB, and TAP2 may predict comorbid disease.
- These genetic findings could serve as prognostic biomarkers and inform personalized treatment strategies.
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