BACKGROUND: 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. OBJECTIVE: We sought to ascertain the genetic risk factors that lead to IgE dysregulation. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: We sought to ascertain the genetic risk factors that lead to IgE dysregulation. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Authors: Y Aron; N Desmazes-Dufeu; R Matran; B S Polla; D Dusser; A Lockhart; E Swierczewski Journal: Clin Exp Allergy Date: 1996-07 Impact factor: 5.018
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Authors: Albert M Levin; Rasika A Mathias; Lili Huang; Lindsey A Roth; Denise Daley; Rachel A Myers; Blanca E Himes; Isabelle Romieu; Mao Yang; Celeste Eng; Julie E Park; Karla Zoratti; Christopher R Gignoux; Dara G Torgerson; Joshua M Galanter; Scott Huntsman; Elizabeth A Nguyen; Allan B Becker; Moira Chan-Yeung; Anita L Kozyrskyj; Pui-Yan Kwok; Frank D Gilliland; W James Gauderman; Eugene R Bleecker; Benjamin A Raby; Deborah A Meyers; Stephanie J London; Fernando D Martinez; Scott T Weiss; Esteban G Burchard; Dan L Nicolae; Carole Ober; Kathleen C Barnes; L Keoki Williams Journal: J Allergy Clin Immunol Date: 2012-11-10 Impact factor: 10.793
Authors: Maria Pino-Yanes; Christopher R Gignoux; Joshua M Galanter; Albert M Levin; Catarina D Campbell; Celeste Eng; Scott Huntsman; Katherine K Nishimura; Pierre-Antoine Gourraud; Kiana Mohajeri; Brian J O'Roak; Donglei Hu; Rasika A Mathias; Elizabeth A Nguyen; Lindsey A Roth; Badri Padhukasahasram; Andres Moreno-Estrada; Karla Sandoval; Cheryl A Winkler; Fred Lurmann; Adam Davis; Harold J Farber; Kelley Meade; Pedro C Avila; Denise Serebrisky; Rocio Chapela; Jean G Ford; Michael A Lenoir; Shannon M Thyne; Emerita Brigino-Buenaventura; Luisa N Borrell; William Rodriguez-Cintron; Saunak Sen; Rajesh Kumar; Jose R Rodriguez-Santana; Carlos D Bustamante; Fernando D Martinez; Benjamin A Raby; Scott T Weiss; Dan L Nicolae; Carole Ober; Deborah A Meyers; Eugene R Bleecker; Steven J Mack; Ryan D Hernandez; Evan E Eichler; Kathleen C Barnes; L Keoki Williams; Dara G Torgerson; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2014-12-06 Impact factor: 10.793