title: Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.
abstract: 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.
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Ferreira
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Vesela
authors.initials: V
authors.lastname: Gateva
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontán
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Ward
authors.initials: W
authors.lastname: Ortmann
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Jorgensen
authors.forename: Björn R
authors.initials: BR
authors.lastname: Ludviksson
authors.forename: Sinikka
authors.initials: S
authors.lastname: Koskinen
authors.forename: Katri
authors.initials: K
authors.lastname: Haimila
authors.forename: Hilary F
authors.initials: HF
authors.lastname: Clark
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005387:Finland; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007055:Iceland; D017098:IgA Deficiency / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D012306:Risk; D013030:Spain; D013548:Sweden; D054928:Validation Studies as Topic
chemical_list: C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1