Journal Article

P62 African-specific IBD susceptibility loci previously identified in African Americans are reflected in patients with IBD in Zambia

Sibwani, Joyce, McGovern, Dermot, Hodges, Phoebe, Mweetwa, Monica, Mengesha, Emebet, Kelly, Paul, Haritunians, Talin

2023

Overview

IntroductionScarcity 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.MethodsSaliva 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.ResultsGenotyping 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.ConclusionsIBD 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.ReferencesBrant 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.Abstract P62 Figure 1Functional pathways with significant associations[Figure omitted. See PDF]

• Publisher: BMJ Publishing Group LTD
• Subject: African Americans / Alleles / Bayesian analysis / Crohn's disease / Diabetes mellitus (insulin dependent) / Environmental factors / Gastroenterology / Gene frequency / Genetic analysis / Genome-wide association studies / Genomes / Genotyping / Haplotypes / Inflammatory bowel disease / Inflammatory bowel diseases / Intestine / NOD2 protein / Population genetics / Saliva / Single-nucleotide polymorphism / Toll-like receptors