Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10(-8)) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10(-11); ATG13-AMBRA1, P = 6.7 × 10(-10); AHI1, P = 8.4 × 10(-10); CLEC16A, P = 1.4 × 10(-9)) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3(+) regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P ≤ 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• celogenomová asociační studie MeSH
• deficience IgA genetika   MeSH
• genetická variace * MeSH
• genové regulační sítě MeSH
• kohortové studie MeSH
• lektiny typu C genetika   MeSH
• lidé MeSH
• proteiny přenášející monosacharidy genetika   MeSH
• proteiny spojené s autofagií genetika   MeSH
• RNA dlouhá nekódující genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH