P62 African-specific IBD susceptibility loci previously identified in African Americans are reflected in patients with IBD in Zambia
Bibliographic record
Abstract
Introduction Scarcity of IBD in sub-Saharan Africa may reflect both differing population genetic disposition and exposure to environmental factors, however, little data relating to this has been published to date. Our aim was to perform genetic analyses of IBD in Zambian subjects. Methods Saliva was collected in Oragene DNA collection tubes (DNAGenotek, Ottawa, Canada) from IBD cases and controls in the GI clinic of a tertiary hospital in Zambia and stored at 4C. DNA was extracted using the NucleoSpin Tissue kit (Macherey-Nagel) and genotyped using the H3Africa Consortium Array (Illumina). Genetic association for genotyped and imputed SNPs case-control binary variable was performed using logistic regression including principal components for population sub-structure as covariates (PLINKv1.9). Variant effect prediction and functional analysis were performed using the Ensembl platform and ClueGO software. Results Genotyping was performed on 16 cases (14 UC, 2 Crohn’s) and 29 controls. Variants were present on LSAMP and ELMO1 which have previously been described as novel risk loci for UC and IBD respectively in African American cohorts.1 2 A variant on IL23R (rs790631:G>A, allele frequency 8.6% cases and 25% controls, (p=3.44 x10-2, OR 0.283)) has previously been associated with increased risk of Crohn’s in a Caucasian population.3 No variants on NOD2, ATG16L1 or CARD9 were present. The SNP with the strongest association with IBD (OR 9.51) was rs3763236:G>A (allele frequency 63.8% cases and 15.6% controls), an intron variant on CNPY3, which encodes a toll-like receptor-specific chaperone protein and has not previously been identified as a risk locus for IBD. Functional pathway analysis (figure 1) shows pathways with significant enrichment which included Type 1 diabetes and the extra-cellular matrix which have previously been implicated in IBD. Conclusions IBD risk loci that have previously been identified as African specific in African American cohorts are reflected in this small cohort of sub-Saharan African patients. These findings suggest that additional and larger studies are needed to determine the genetic architecture of under researched populations in which IBD is emerging. References Brant SR, Okou DT, Simpson CL, Cutler DJ, Haritunians T, Bradfield JP, et al. Genome-wide association study identifies African-specific susceptibility loci in African Americans with inflammatory bowel disease. Gastroenterology. 2017;152(1):206–17.e2. Cordero RY, Cordero JB, Stiemke AB, Datta LW, Buyske S, Kugathasan S, et al. Trans-ancestry, bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian, and European cohort. Hum Mol Genet. 2022. Taylor KD, Targan SR, Mei L, Ippoliti AF, McGovern D, Mengesha E, et al. IL23R haplotypes provide a large population attributable risk for Crohn’s disease. Inflamm Bowel Dis. 2008;14(9):1185–91.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.003 | 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".