ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 153

Identification Of Autoimmune Disease Risk Alleles That Are Under Recent Selection In The Sea Island Gullah African Americans

Carl D. Langefeld1, Satria Sajuthi1, Jasmin Divers1, Yiqi Huang2, Uma Nayak3, Wei-Min Chen3, Kelly J. Hunt4, Diane L. Kamen5, Gary S. Gilkeson6, Jyotika K. Fernandes7, Ida J. Spruill7, W. Timothy Garvey8, Michèle M. Sale2 and Paula S. Ramos5, 1Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 2Department of Medicine and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 3Public Health Sciences, University of Virginia, Charlottesville, VA, 4Public Health Sciences, Medical University of South Carolina, Charleston, SC, 5Department of Medicine, Medical University of South Carolina, Charleston, SC, 6Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC, 7Medical University of South Carolina, Charleston, SC, 8Department of Nutrition Sciences and Birmingham VA Medical Center, University of Alabama at Birmingham, Birmingham, AL

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Genetics and Genomics of Rheumatic Disease I

Session Type: Abstract Submissions (ACR)

Background/Purpose: The reasons for the ethnic disparities in rheumatic and autoimmune diseases (AIDs) are largely unknown. Given the increasing evidence of selection at loci associated with human diseases, identification of alleles under selection may provide further insight into disease susceptibility. The Gullahs form a unique population of African ancestry in the U.S. In addition to their relative genetic and environmental homogeneity and low European admixture, a shorter genetic distance between the Gullahs and Sierra Leoneans has also been reported, suggesting that population genetic signals, such as regions under recent selection, may be more easily detected in the Gullahs than in other African American (AA) populations. We sought to capitalize upon the relative closeness between the Gullah and Sierra Leoneans to identify regions that differentiate both populations and may hence be under recent population-specific selective pressures. The goal of this study was to identify regions that might be under recent positive selection in the Gullah and that harbor risk loci for AIDs, which may help explain the higher prevalence of autoimmunity in AA. 

Methods: We computed a linear regression model using the principal component of the HapMap Yoruba (YRI) population from Nigeria (PC2) as a quantitative outcome, using 277 Gullah and 400 Sierra Leonean samples genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0. We adjusted for European admixture via inclusion of the HapMap Caucasian (CEU) population component (PC1) as a covariate. In total, 679,513 SNPs with MAF>5% were used in this analysis. In order to exclude spurious loci, only regions where at least one SNP met genome-wide significance (P<5E-10) and a second significant SNP (PResults: Nine regions met our criteria as those that best differentiate the Gullah from the Sierra Leonean. The most significant was a ~2 Mb region at Xq22.2-q22.3 around the IL1RAPL2 gene, where 4 SNPs had P<5E-10. Of the other 8 regions, half encompass immune-function genes: TLR3 at 4q35.1, CD83 at 6p23, the extended HLA at 6p22.1-21.32, and RAPGEF5-IL6 at 7p15.3. The CD83 region is associated with rheumatoid arthritis, the HLA region with all AIDs, and the RAPGEF5-IL6 region with dialysis-related mortality in AA and CRP levels.

Conclusion: We have identified several regions that harbor immune function genes and differentiate the Gullah from the Sierra Leoneans, suggesting that recent selection may be operating at these loci. Given the relative homogeneity of the Gullah and their genetic proximity to Africans from Sierra Leone, identification of regions that might be under selection and harbor immune-related genes in the Gullah has the potential to elucidate AID risks in AA.

Disclosure:

C. D. Langefeld,
None;

S. Sajuthi,
None;

J. Divers,
None;

Y. Huang,
None;

U. Nayak,
None;

W. M. Chen,
None;

K. J. Hunt,
None;

D. L. Kamen,
None;

G. S. Gilkeson,
None;

J. K. Fernandes,
None;

I. J. Spruill,
None;

W. T. Garvey,
None;

M. M. Sale,
None;

P. S. Ramos,
None.

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