Small Bowel Location, Stricturing Behavior, Vitamin D Receptor Polymorphism, and Metabolic Disease Susceptibility Genes Are Associated With NAFLD in Crohn’s Disease
Bibliographic record
Abstract
Introduction: The relationship between metabolic syndromes and IBD is complex; there are shared susceptibility genes; abnormal fat deposition in CD with pro-inflammatory effects; and a reported NAFLD prevalence of 8% in IBD compared to 30% of the ‘healthy’ U.S. population. Our aim was to investigate the prevalence of NAFLD in a tertiary referral center and investigate clinical, serologic, and genetic associations with NAFLD in IBD patients. Methods: Patients included in our IBD repository with abdominal imaging were eligible for inclusion. Charts, CT, and U.S. reports were reviewed to determine NAFLD status. Demographic, and clinical (Montreal classification, BMI), characteristics were obtained by chart review. Serology data (ASCA, OMPc, CBir1, anti-I2 & ANCA) were generated. Genotyping was performed by Illumina technology including genome-wide and immunochip platforms. Standard statistical tests were used to test for association with appropriate correction for population structure. Results: In 1,304 IBD cases (71% CD, 29% UC/IBDU) we observed an NAFLD prevalence of 9.7%. The Prevalence of NAFLD in CD and UC was similar. NAFLD IBD patients had increased BMI (p<2.2E-16). Table 1 shows CD phenotypic associations with NAFLD. NAFLD was not associated with disease extent in UC. There were no significant associations with NAFLD for age of IBD onset, gender, need for surgery, or smoking. In CD, we observed a strong correlation between anti-I2 level (p=0.005) and anti-I2 status (p=0.003) and NAFLD. In UC, ASCA IgG level was associated with NAFLD (p=0.001). CD serological quartile sum analyses revealed a trend towards association with NAFLD (p=0.06). Immunochip analyses revealed association with: metabolic disease genes (LECT2 (hepatokine linking obesity to insulin resistance), CCR5, CAMTA1, GRIP1) and other immune disease loci (TNFRSF1A, IRAK3) with p-values<10 (-5); as well as known IBD genes (CDKAL1, CALM3, vitamin D receptor (VDR), GPR183, IFNGR2/IL10RB (all p<0.05)). GWAS analyses revealed 4 loci p<10 (-5) including MYO5A (an insulin target in adipose tissue) and genes highly expressed in liver (SNTG2). These genes implicate insulin resistance and metabolic disease pathways in NAFLD development in IBD.Table 1: IBD Phenotypic Associations With NAFLDConclusion: NAFLD is associated with raised BMI and metabolic disease genes in IBD as well as stricturing small bowel disease and anti-I2 in CD. These findings may help identify IBD patients at risk of hepatotoxicity from medications such as methotrexate. Further work understanding this relationship is warranted.
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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 | 0.001 | 0.001 |
| 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) | 0.004 | 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".