A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study

Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation. We sought to ascertain the genetic risk factors that lead to IgE dysregulation. A genome-wide association st...

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Vydáno v:	Journal of allergy and clinical immunology Ročník 129; číslo 3; s. 840 - 845.e21
Hlavní autoři:	Granada, Mark, Wilk, Jemma B., Tuzova, Marina, Strachan, David P., Weidinger, Stephan, Albrecht, Eva, Gieger, Christian, Heinrich, Joachim, Himes, Blanca E., Hunninghake, Gary M., Celedón, Juan C., Weiss, Scott T., Cruikshank, William W., Farrer, Lindsay A., Center, David M., O'Connor, George T.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York, NY Mosby, Inc 01.03.2012 Elsevier Elsevier Limited
Témata:	Adult Allergies Allergy and Immunology asthma atopy Biological and medical sciences blood groups Cardiovascular Diseases - blood Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Cardiovascular Diseases - immunology chemokine receptors childhood Chronic obstructive pulmonary disease, asthma Cohort Studies Female Fundamental and applied biological sciences. Psychology Fundamental immunology Genes Genetic Predisposition to Disease Genome-Wide Association Study heart HLA Antigens - genetics Humans Hypersensitivity - blood Hypersensitivity - epidemiology Hypersensitivity - genetics Hypersensitivity - immunology immunoglobulin E Immunoglobulin E - blood Immunopathology Interleukin-13 - genetics Linkage Disequilibrium loci Male Medical research Medical sciences meta-analysis Middle Aged pathogenesis Plasma Pneumology Polymorphism, Single Nucleotide Receptors, IgE - genetics Risk Factors Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis signal transduction single nucleotide polymorphism STAT6 Transcription Factor - genetics Studies Total IgE transcription factors United Kingdom United States B58C GWAS atopy asthma FHS KORA DARC CEU RAD50 SNP genome-wide association study LD Total IgE MACH STAT6 CAMP Linkage disequilibrium Signal transducer and activator of transcription 6 Markov Chain haplotyping Duffy blood group, chemokine receptor RAD50 homolog (Saccharomyces cerevisiae) Childhood Asthma Management Program Framingham Heart Study Western European British 1958 Birth Cohort Cooperative Health Research in the Region of Augsburg Single nucleotide polymorphism Heart Allergy Lung disease Immunopathology Respiratory disease IgE Concentration Asthma Atopy Blood plasma Association Immunology Bronchus disease Circulatory system Obstructive pulmonary disease Genome
ISSN:	0091-6749, 1097-6825, 1097-6825
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Shrnutí:	Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation. We sought to ascertain the genetic risk factors that lead to IgE dysregulation. A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS). Seventy of the top single nucleotide polymorphisms (SNPs) were selected based on P values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with 5 independent populations from the Cooperative Health Research in the Region of Augsburg cohort, the British 1958 Birth Cohort, and the Childhood Asthma Management Program cohort. Thirteen SNPs located in the region of 3 genes, FCER1A, signal transducer and activator of transcription 6 (STAT6), and IL13, were found to have genome-wide significance in the FHS cohort GWAS. The most significant SNPs from the 3 regions were rs2251746 (FCER1A, P = 2.11 × 10−12), rs1059513 (STAT6, P = 2.87 × 10−8), and rs1295686 (IL13, P = 3.55 × 10−8). Four additional gene regions, HLA-G, HLA-DQA2, HLA-A, and Duffy blood group, chemokine receptor (DARC), reached genome-wide statistical significance in a meta-analysis combining the FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene. This GWAS of the FHS cohort has identified genetic loci in HLA genes that might have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of the known susceptibility loci FCER1A, STAT6, and IL13 for the dysregulation of total IgE.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0091-6749 1097-6825 1097-6825
DOI:	10.1016/j.jaci.2011.09.029