Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population

Tiina M. Järvinen, Anna Hellquist, Marco Zucchelli, Sari Koskenmies, Jaana Panelius, Taina Hasan, Heikki Julkunen, Mauro D'Amato, Juha Kere

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Objective: A large number of genes, including several not previously implicated in SLE susceptibility, have recently been identified or confirmed by genome-wide association studies (GWAS). In this study, we sought to replicate some of these results in Finnish SLE patients (n = 275) and control individuals (n = 356). Methods: We genotyped 32 single nucleotide polymorphisms (SNPs) in 12 of the best-supported GWAS-identified SLE genes and loci. We further investigated gene-gene interactions between the loci included in the study. Results: The strongest evidence of association was found at the IRF5-TNPO3 locus, with the most significant P-value being 2.0×10 -7 and an odds ratio of 1.95 (95% CI 1.51, 2.50). Association between SLE and TNFAIP3, FAM167A-BLK, BANK1 and KIAA1542 was also confirmed, although at a lower significance level and contribution to individual risk. No significant association was found with 1q25.1, PXK, ATG5, ICA1, XKR6, LYN and SCUBE1. Furthermore, no significant gene-gene interactions were detected. Conclusion: Replication of previous GWAS findings across diverse populations is of importance to validate these associations and to get a better understanding of potential genetic heterogeneity between populations in SLE susceptibility. Our results attest the importance of B-cell receptor pathway and IFN signalling in SLE pathogenesis.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
Issue number1
Publication statusPublished - 1 Jan 2012
Externally publishedYes


  • B-cell receptor pathway
  • Epistasis
  • Finnish population
  • Genome-wide association study replication
  • Interferon regulatory factor 5-transportin 3

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