P1169 Multimorbidity and Disease Trajectories in Patients with INFLAMMATORY BOWEL DISEASES: Insights from Observational and Genetic Analyses
Bibliographic record
Abstract
Abstract Background The multi-morbidity pattern of inflammatory bowel disease (IBD) remains under-explored. We integrated both observational and genetic data to elucidate multisystem comorbidities and health consequences of IBD. Methods Phenome-wide association study (PheWAS) based on the international classification of disease (ICD)-diagnosed IBD was conducted to explore its associations with 1,053 unique clinical outcomes in the UK Biobank. Disease trajectory analyses were implemented to illustrate sequential patterns of IBD-related comorbidities. The associations of genetic liability to IBD proxied by a polygenic score with identified clinical outcomes were examined to strengthen causality (N=385,917). To investigate potential shared genetic bases and causality, we performed a cross-trait linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (TSMR) analysis using the FinnGen biobank (N=377,277). The impact of IBD subtypes and the age at diagnosis were also evaluated in sensitivity analyses. Results A total of 5,782 cases with IBD (3,940 cases with UC and 1,800 cases with CD) were diagnosed at baseline in the UK Biobank. Observational PheWAS revealed elevated risks of all-cause mortality with HRs of 1.34 (95%CI=1.24-1.45, P<0.001), 1.61 (95%CI=1.41-1.83, P<0.001) and 1.22 (95%CI=1.10-1.34, P<0.001) for patients with IBD, CD or UC respectively. Increased mortality risk was noted across pediatric, early-onset, and later-onset IBD patients. Sequential patterns of IBD-related comorbidities were primarily found in cardiometabolic, respiratory, digestive and autoimmune diseases. The polygenic PheWAS, LDSC and TSMR analyses supported both strong genetic correlations and causal associations of IBD with immune-mediated (notably psoriatic arthropathies, psoriasis, dermatitis, asthma) as well as non-autoimmune diseases ( pneumonia, anemias, and renal failure). Conclusion Our observational and genetic analyses suggest multisystem comorbidities and consequences of IBD, highlighting the need for multidisciplinary clinical management and investigation of shared biologically or genetically regulated mechanisms in the pathogenesis of IBD.
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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 | 0.004 | 0.017 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".