Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency

Ricardo C. Ferreira, Qiang Pan-Hammarström, Robert R. Graham, Vesela Gateva, Gumersindo Fontán, Annette T. Lee, Ward Ortmann, Elena Urcelay, Miguel Fernández-Arquero, Concepción Núnez, Gudmundur Jorgensen, Björn R. Ludviksson, Sinikka Koskinen, Katri Haimila, Hilary F. Clark, Lars Klareskog, Peter K. Gregersen, Timothy W. Behrens*, Lennart HammarströM

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)


To understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1, 090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10-10) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10-7), and 29 additional loci were identified with P < 5 x 10-5. A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10-4) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD.

Original languageEnglish
Pages (from-to)777-782
Number of pages6
JournalNature Genetics
Issue number9
Publication statusPublished - Sept 2010


Dive into the research topics of 'Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency'. Together they form a unique fingerprint.

Cite this