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Replication of genomewide associations with allergic sensitization and allergic rhinitis

机译：与过敏性敏化和过敏性鼻炎的基因组关联的复制

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摘要

Background Three genomewide metastudies have recently reported associations with self-reported allergic rhinitis and allergic sensitization. The three studies together identified a set of 37 loci but showed low concordance. This study investigates the reproducibility of the detected single nucleotide polymorphism (SNP) associations in an extensively characterized longitudinal cohort, BAMSE.Methods Phenotypic evaluation of allergic rhinitis (AR) and allergic sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age. Allele frequencies of 39 SNPs were investigated for association with the exact allergic phenotypes of the metastudies. Odds ratios and false discovery rates were calculated, and the impact of asthma was evaluated. The cases were also evaluated for age at onset effects (≤ or >8 years of age).Results Association tests of the 39 SNPs identified 12 SNPs with P-values < 0.05 and Q-values < 0.10. Two of the four loci (TLR6-TLR1 and HLA-DQA1-HLA-DQB1) identified in all three original studies were also identified in this study. Three SNPs located in the TLR6-TLR1 locus had the lowest P-values and Q-values < 0.1 when using a well-defined AR phenotype. Two loci showed significant age at onset effects, but the effect of asthma on the associations was very limited.Conclusion The TLR6-TLR1 locus is likely to have a central role in the development of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis.
机译：背景技术三个基因面重塑最近报告了具有自我报告的过敏性鼻炎和过敏性敏化的关联。这三项研究共同确定了一组37个基因座，但表现出低的一致性。本研究调查了在广泛表征纵向队列中检测到的单核苷酸多态性（SNP）关联的再现性，BAMSE.MSE.METHODS对过敏性鼻炎（AR）的表型评估，在853名来自BAMSE的2153名儿童上进行过敏性敏化性。研究了39个SNP的等位基因频率与转移的确切过敏表型相关联。计算差距和假发现率，评价哮喘的影响。还评估了发病效应的年龄（≤或> 8岁）的病例。结果，39 SNP的关联测试识别12个SNP，具有p值<0.05和Q值<0.10。在本研究中还发现了在所有三项原始研究中鉴定的四个基因座（TLR6-TLR1和HLA-DQA1-HLA-DQB1中的两个。位于TLR6-TLR1基因座中的三个SNP在使用明确定义的AR表型时具有最低的P值和Q值<0.1。两个基因座表现出显着的效果年龄，但哮喘对关联的影响非常有限。结论TLR6-TLR1基因座可能在过敏性疾病的发展中具有核心作用。 SSTR1-MIPOL1和TSLP-SLC25A46遗传变异之间的关联和发病时的年龄是在过敏性鼻炎中发病效应的第一个年龄报告。

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  • 来源
    《Allergy》 |2014年第11期|共9页
  • 作者

    NilssonD.; HenmyrV.; HalldénC.; S?llT.; KullI.; WickmanM.; MelénE.; CardellL.O.;

  • 作者单位

    Division of ENT Diseases CLINTEC Karolinska Institutet HuddingeStockholm Sweden Biomedicine;

    Division of ENT Diseases CLINTEC Karolinska Institutet HuddingeStockholm Sweden Biomedicine;

    Biomedicine Kristianstad UniversityKristianstad Sweden;

    Department of Biology Lund UniversityLund Sweden;

    Biomedicine Kristianstad UniversityKristianstad Sweden Department of Clinical Science and;

    Institute of Environmental Medicine Karolinska InstitutetStockholm Sweden Sachs Children's;

    Institute of Environmental Medicine Karolinska InstitutetStockholm Sweden Sachs Children's;

    Division of ENT Diseases CLINTEC Karolinska Institutet HuddingeStockholm Sweden;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    age-dependent effect; allergic rhinitis; allergic sensitization; association study; TLR6-TLR1 locus;

    机译：年龄依赖性效果;过敏性鼻炎;过敏性敏化;协会研究;TLR6-TLR1基因座;

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