A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease
Bibliographic record
Abstract
BACKGROUND: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence. STUDY DESIGN: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at 8 loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively. RESULTS: One hundred and ninety-one patients with Crohn's disease and 11.2 years mean postoperative follow-up were included. Forty-six percent experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3 years; p = 0.03); inflammatory disease behavior was associated with a lower chance of repeat operation (p < 0.01). Of the loci assessed on multivariable analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p < 0.05). CONCLUSIONS: We identify BACH2 as a susceptibility locus for postoperative recurrence of Crohn's disease in our cohort. BACH2 is critical in the differentiation and function of T cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in postoperative Crohn's disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".