A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.

Academic Article


  • Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
  • Published In

  • Nature Genetics  Journal
  • Keywords

  • DNA Replication, DNA-Binding Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Interleukin-10, Lupus Erythematosus, Systemic, Neoplasm Proteins, Polymorphism, Single Nucleotide, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins, Risk Factors
  • Digital Object Identifier (doi)

    Author List

  • Gateva V; Sandling JK; Hom G; Taylor KE; Chung SA; Sun X; Ortmann W; Kosoy R; Ferreira RC; Nordmark G
  • Start Page

  • 1228
  • End Page

  • 1233
  • Volume

  • 41
  • Issue

  • 11