ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2274

Genes Associated with Systemic Lupus Erythematosus Show Evidence of Selection in the Gullah African American Population

Paula S. Ramos1, Satria Sajuthi2, Yiqi Huang3, Diane L. Kamen4, Jasmin Divers2, Kenneth M. Kaufman5, John B. Harley6, Robert P. Kimberly7, Carl D. Langefeld2, Michèle M. Sale3, W. Timothy Garvey8 and Gary S. Gilkeson9, 1Department of Medicine, Medical University of South Carolina, Charleston, SC, 2Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 3Department of Medicine and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 4Department of Medicine, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Charleston, SC, 51Center for Autoimmune Genomics and Etiology and Rheumatology Division, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati, Cincinnati, OH, 6Division of Rheumatology and The Center for Autoimmune Genomics & Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 7Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 8Department of Nutrition Sciences and Birmingham VA Medical Center, University of Alabama at Birmingham, Birmingham, AL, 9Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

In spite of its higher prevalence and severity, little is known about the genetic etiology of systemic lupus erythematosus (SLE) in African Americans (AA). Given this greater prevalence and the increasing evidence of selection at loci associated with human diseases, identification of alleles under selection may provide insight into the susceptibility to SLE. The Gullah are an AA population with limited and well defined ancestral diversity. The shorter genetic distance between the Gullah and Sierra Leonean (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. Since population-specific selection may cause allele frequency differences, the goal of this study was to identify regions with minor allele frequency (MAF) differences between Gullah and SL that may increase the risk of SLE in AA.

Methods:

We had available 120 Gullah and 400 SL samples, all unaffected, genotyped on the Illumina 1M and Affymetrix SNP Array 6.0, respectively. After stringent quality control was applied to each population, 185,569 SNPs common to both arrays with MAF>5% were used to compute the significance of the MAF differences between the two populations. In order to exclude spurious signals, only regions where at least two SNPs in linkage disequilibrium showed significant Bonferroni-adjusted MAF differences were considered.

Results: Amongst the regions where multiple SNPs showed significant MAF differences between the Gullah and SL (PCSMD1 gene, which has been associated with, among other traits, emphysema, multiple sclerosis, and insulin resistance in AA. Overall, our results confirmed an enrichment of genes involved in immunity and defense (BP00148; P=0.0076).

Conclusion: We have identified several regions with significant allele frequency differences between the Gullah and SL, suggesting that population-specific selective pressures may be operating at these loci. Given the increased prevalence of SLE in AA and the homogeneity of the Gullah, identification of these regions in the Gullah has the potential to elucidate the etiology of SLE in AA.

Disclosure:

P. S. Ramos,
None;

S. Sajuthi,
None;

Y. Huang,
None;

D. L. Kamen,
None;

J. Divers,
None;

K. M. Kaufman,
None;

J. B. Harley,
None;

R. P. Kimberly,
None;

C. D. Langefeld,
None;

M. M. Sale,
None;

W. T. Garvey,
None;

G. S. Gilkeson,
None.

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