Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: The reasons for the ethnic disparities in rheumatologic and autoimmune diseases (ADs) are largely unknown. We posit that population-specific selection influencing the allele frequencies at some loci contribute to ethnic disparities. Relative to other African-Americans (AA), the Gullah population of coastal South Carolina and Georgia has lower European admixture and higher ancestral homogeneity from the Sierra Leone (SL) area in West Africa. The shorter genetic distance between the Gullah and SL suggests that population genetic signals, such as regions under recent selection, may be more easily detected in the Gullah than in other AA populations. We sought to leverage the relative closeness between the Gullah and SL to identify autoimmune risk alleles with evidence of population differentiation that may result from geographically restricted, subtle selective pressure.
Methods: We computed the fixation index (FST) between populations, a measure of population differentiation that measures the degree of genetic differentiation at a locus. Using genome-wide genotype data on 277 healthy Gullah, 400 SL, and 203 YRI from the HapMap3 Project, we computed the Weir and Cockerham’s (1984) FST (in VCFTOOLS) and the Hudson estimator for FST (in EIGENSOFT) between Gullah and SL, and Gullah and YRI. A total of 582,100 autosomal SNPs met standard GWAS quality control. We prioritized variants in the top 0.01% of highest FST between populations, then selected gene regions where at least another variant was in the top 0.1% of highest FST. For these genes, trait associations were compiled from the NHGRI-EBI GWAS Catalog, and Ingenuity Pathway Analysiswas used to identify significant pathways and biological functions among the top genes.
Results: Although the low FST estimates between the Gullah and their ancestors supports their genetic proximity (FST=0.003), the loci in the top 0.01% of highest FST were different between Gullah and SL, and between Gullah and YRI. While the loci with highest FST between Gullah and SL were enriched for genes involved in Cellular Function and Maintenance (P=6.1E-04), the top genes between Gullah and YRI were enriched for Cancerfunctions (P=4.1E-04). Although only a small fraction of the genes have been reported as associated with an AD, the most significant pathways were immune-related, for both the genes showing population differentiation between Gullah and SL (antigen presentation, P=4.9E-04; allograft rejection signaling, P=8.3E-04), and between Gullah and YRI (CCR3 signaling in eosinophils, P=4.8E-04; role of NFAT in regulation of the immune response, P=1.5E-03).
Conclusion: We identified several regions that show evidence of selection in the Gullah, including the HLA and CD36, which are known to be under selection that happened pre-admixture. The paucity of genes associated with ADs might be due to the lack of genetic association studies in AA. The enrichment of immune pathways suggests that autoimmune risk alleles might be present in the Gullah, as well as other AA. Given the increased prevalence of several ADs in AA, identification of regions under selection in the Gullah can further the understanding of the natural history and disease risks in AA and help explain the ethnic disparity.
To cite this abstract in AMA style:Ramos PS, Sajuthi S, Chen WM, Divers J, Fernandes JK, Gilkeson GS, Hunt KJ, Kamen DL, Nayak U, Garvey WT, Sale MM, Langefeld CD. Enrichment of Immune Pathways in Genes Under Geographically Restricted Adaptation in the Gullah African American Population of South Carolina [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/enrichment-of-immune-pathways-in-genes-under-geographically-restricted-adaptation-in-the-gullah-african-american-population-of-south-carolina/. Accessed December 1, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/enrichment-of-immune-pathways-in-genes-under-geographically-restricted-adaptation-in-the-gullah-african-american-population-of-south-carolina/