Join us for the next instalment of the STAGE International Speaker Seminar Series (ISSS) with
Carl Langefeld
Professor, Department of Biostatistical Sciences
Co-Director, Bioinformatics Core
Wake Forest Comprehensive Cancer Center
Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (~50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5x10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. The majority of the SLE-risk alleles show increased European ancestry, suggesting increased likelihood of EA origins. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE
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