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Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study
- Source :
- Petri, M., Epidemiology of systemic lupus erythematosus (2002) Best Pract. Res. Clin. Rheumatol., 16, pp. 847-858, Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario
- Publication Year :
- 2012
-
Abstract
- Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p meta-Euro = 2.08 × 10 -10), transmembrane protein 39A (TMEM39A; rs1132200; p meta-all = 8.62 × 10 -9), and 17q21 (rs1453560; p meta-all = 3.48 × 10 -10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10 -8 < p meta-Euro < 9.99 × 10 -5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. © 2012 The American Society of Human Genetics.
- Subjects :
- Male
Chromosome 17Q
Hispanic
Ikzf3 Gene
Genetic Susceptibility
Gene
Genetic Risk
Or8D4 Gene
Indians
Lpp Gene
Ethnicity
Haplotype
African American
European American
Membrane Protein
Immune Response
Irf8 Gene
African Continental Ancestry Group
Transmembrane Protein 39A
Cadm2 Gene
C1Orf64 Gene
Chromosome Mapping
Fam19A2 Gene
Patología
Single Nucleotide
Slu7 Gene
Tmem39A Gene
Genetic Predisposition To Disease
High Risk Population
Interferon Consensus Sequence Binding Protein
Gene Locus
Zpbp2 Gene
Genetic Variability
American Indian
Interferon Regulatory Factors
Priority Journal
Interferon
Female
Hispanic Americans
Sequence Analysis
Genetic Association
North American
Human
Asian Continental Ancestry Group
Gene Sequence
Genotype
Major Clinical Study
European Continental Ancestry Group
Protein Ikzf3
Il12A Gene
Loc6392 Gene
Systemic Lupus Erythematosus
Article
Heritability
Ikaros Transcription Factor
Unclassified Drug
Autoantigen
Lupus eritematoso sistémico
Humans
Zona Pellucida Binding Protein 2
Controlled Study
Gene Identification
Polymorphism
Cfhr1 Gene
Asian
Environmental Factor
Lupus Erythematosus
Gene Mapping
Egg Proteins
Systemic
Immunoregulation
Membrane Proteins
Dna
Genome Analysis
Genética
Haplotypes
Stxbp6 Gene
Single Nucleotide Polymorphism
Adamtsl1 Gene
Immunological Tolerance
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Petri, M., Epidemiology of systemic lupus erythematosus (2002) Best Pract. Res. Clin. Rheumatol., 16, pp. 847-858, Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario
- Accession number :
- edsair.od......3056..7ac8f8447602907e0016c2a2c6b11ad4