| Title: | Clonal hematopoiesis of indeterminate potential and risk of incident Crohn's disease - a prospective cohort study |
| Journal: | Journal of Crohn's and Colitis |
| Published: | 13 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40651007/ |
| DOI: | https://doi.org/10.1093/ecco-jcc/jjaf118 |
Publication 16987
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Abstract
BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic, immune-mediated inflammatory disorder. Its pathophysiology involves dysregulation of both innate and adaptive immune responses, which can occur in clonal hematopoiesis of indeterminate potential (CHIP) individuals. Therefore, we hypothesize that CHIP may influence CD incidence. However, no study has explored the association between CHIP and incident CD. We analyzed UK Biobank data to investigate the association between CHIP and incident CD.</p>
METHODS: CHIP was defined based on whole-exome sequencing data. The outcome was incident CD. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for CD in relation to CHIP.</p>
RESULTS: This study included 461 913 participants, of whom 14 339 (3.1%) had CHIP. The incidence rate of CD was 21.6 and 37.7 per 100 000 person-years for individuals without and with CHIP, respectively. We found a statistically significant increased risk of CD among individuals with CHIP (HR, 1.68; 95% CI, 1.30-2.16), compared with the reference group. This association was particularly stronger in individuals with JAK2-mutant CHIP (HR, 7.28; 95% CI, 1.82-29.13), ASXL1-mutant CHIP (HR, 3.07; 95% CI, 1.74-5.44), and DNMT3A-mutant CHIP (HR, 1.73; 95% CI, 1.24-2.42). Additionally, the association did not vary greatly by demographic, socioeconomic, lifestyle factors, CHIP clone size, or cancer comorbidity.</p>
CONCLUSIONS: CHIP was associated with a markedly increased risk of subsequent CD. The association was particularly stronger in JAK2-mutant CHIP, ASXL1-mutant CHIP, and DNMT3A-mutant CHIP. The findings of this study may offer potential insights for future investigations into the mechanistic underpinnings of CD.</p>
17 Keywords
- Adult
- Clonal Hematopoiesis
- Crohn Disease
- DNA (Cytosine-5-)-Methyltransferases
- DNA Methyltransferase 3A
- Exome Sequencing
- Female
- Humans
- Incidence
- Janus Kinase 2
- Male
- Middle Aged
- Mutation
- Prospective Studies
- Repressor Proteins
- Risk Factors
- United Kingdom
7 Authors
- Yuqing Wang
- Huiwen Xue
- Ola Olén
- Åsa H Everhov
- Hui Wei
- Qifa Liu
- Qianwei Liu
1 Application
| Application ID | Title |
|---|---|
| 106912 | Comprehensive investigation of biomarkers and medical conditions in relation to subsequent hematological disorders or cancer |
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