Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations which are known to vary in severity by race. Health disparities in prognosis and and presentation of SLE place a disproportionate burden on underrepresented populations as non-white populations with SLE are more likely to have features indicative of more severe disease. Prior analyses have shown global ancestry is associated with SLE risk and SLE features such as lupus nephritis; however, it is not yet known if local genetic ancestry is associated with specific SLE manifestations.
Methods: We evaluated local ancestry in multi-ethnic SLE cohorts from the UCSF Lupus Genetics Study and the California Lupus Epidemiology Study (CLUES). Genetic and phenotype data were available for 250 African American, 288 Asian, and 232 Hispanic subjects. All subjects satisfied the American College of Rheumatology criteria for SLE. DNA was extracted from blood or saliva samples and genotyped on the Affymetrix LAT1 World Array, which is designed specifically for diverse ethnic populations. Genotype data were imputed using IMPUTE4 and phased using BEAGLEv5.1. We inferred local ancestry using RFMix2.0, which assigns local ancestry proportions to windows of the genome, and analyzed differences in local ancestry within each population. We used a non-parametric test statistic (Montana and Pritchard) to assess the difference in local ancestry between cases and controls at a SNP while adjusting for global ancestry differences. We assessed differences for two key features of SLE including if a subject had been diagnosed with lupus nephritis and age of symptom onset. We conducted tests both genome-wide and for candidate SLE SNPs previously identified to be associated with SLE and lupus nephritis risk.
Results: Although results did not remain significant after adjustment for multiple testing, top results (nominal p< 0.01) for differences in African Americans with lupus nephritis showed increased African ancestry at SNPs located in TTYH2, which functions in chloride anion channels and may play a role in kidney tumorigenesis. SNPs located in SGCN, which encodes a calcium binding protein, showed increased African and Asian ancestry in both African American and Asian subjects with lupus nephritis, respectively. In Hispanic subjects, increased Amerindian ancestry at a SNP previously associated with SLE risk in DGKQ was associated with an earlier age of onset.
Conclusion: These results warrant further investigation into local genetic ancestry differences to determine if these differences may contribute to health disparities for admixed patients with SLE.
To cite this abstract in AMA style:Solomon O, Lanata C, Adams C, Nititham J, Taylor K, Chung S, Pons-Estel B, Tusié-Luna T, Tsao B, Morand E, Alarcón-Riquelme M, Barcellos L, Criswell L. Local Genetic Ancestry Associations with Clinical Features of Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/local-genetic-ancestry-associations-with-clinical-features-of-systemic-lupus-erythematosus/. Accessed November 26, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/local-genetic-ancestry-associations-with-clinical-features-of-systemic-lupus-erythematosus/