Document Detail


Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.
MedLine Citation:
PMID:  20694011     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Ricardo C Ferreira; Qiang Pan-Hammarström; Robert R Graham; Vesela Gateva; Gumersindo Fontán; Annette T Lee; Ward Ortmann; Elena Urcelay; Miguel Fernández-Arquero; Concepción Núñez; Gudmundur Jorgensen; Björn R Ludviksson; Sinikka Koskinen; Katri Haimila; Hilary F Clark; Lars Klareskog; Peter K Gregersen; Timothy W Behrens; Lennart Hammarström
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-08
Journal Detail:
Title:  Nature genetics     Volume:  42     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-09-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  777-80     Citation Subset:  IM    
Affiliation:
Genentech, Inc., South San Francisco, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Autoimmune Diseases / complications,  genetics
Autoimmunity / genetics*
Case-Control Studies
DEAD-box RNA Helicases / genetics*
Finland
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Iceland
IgA Deficiency / etiology,  genetics*,  immunology
Linkage (Genetics)
Risk
Spain
Sweden
Validation Studies as Topic
Grant Support
ID/Acronym/Agency:
AR043274/AR/NIAMS NIH HHS; R01NS057756/NS/NINDS NIH HHS; U19 AI067152/AI/NIAID NIH HHS; U24 NS051869/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
EC 3.6.1.-/DEAD-box RNA Helicases; EC 3.6.1.-/IFIH1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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