期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 127, 期 1, 页码 223-U358出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.10.006
关键词
Atopy; specific IgE; skin prick test; genome-wide association study; British 1958 Birth Cohort
资金
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02, 079895]
- Juvenile Diabetes Research Foundation International
- National Institute for Health Research Cambridge Biomedical Research Centre
- Asthma UK
- British Lung Foundation
- Asthma, Allergy, and Inflammation Research (AAIR)
- Medical Research Council (UK)
- [U01 DK062418]
- Medical Research Council [G0600705, G0800582, G1001799, G9815508] Funding Source: researchfish
- Asthma UK [05/055] Funding Source: researchfish
- MRC [G1001799, G0600705, G0800582, G0000934] Funding Source: UKRI
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK062418] Funding Source: NIH RePORTER
Background: A genetic component in the development of atopy has been identified. However, numerous heritability models have been proposed with inconsistent replication of susceptibility loci and genes. Objective: We sought to use a genome-wide association study approach to examine genetic susceptibility to atopy, which was defined as increased specific IgE levels, positive skin prick test (SPT) responses, or both, within a large discovery cohort and 3 additional white populations. Methods: Single nucleotide polymorphisms (SNPs) across the genome were tested for association with increased specific IgE levels (>= 0.35 kU(A)/L) in the British 1958 Birth Cohort (1083 cases and 2770 control subjects; Illumina 550K Array) to 1 or more allergens, including house dust mite (Der p 1), mixed grass, or cat fur. Independent replication of identified loci (P <= .05) was assessed in 3 case-control cohorts from the United Kingdom (n = 3225). Combined analyses of data for top signals across cohorts were conducted for atopic phenotypes: increased specific IgE levels (1378 cases and 3151 control subjects) and positive SPT responses (1058 cases and 2167 control subjects). Results: A single SNP on chromosome 13q14 met genome-wide significance (P = 2.15 x 10(-9)), and a further 6 loci (4.50 x 10(-7) <= P <= 5.00 x 10(-5)) showed weaker evidence for association with increased specific IgE levels in the British 1958 Birth Cohort. However, no SNPs studied showed consistent association with atopy defined by increased specific IgE levels, positive SPT responses, or both in all study cohorts. Conclusions: Seven putative atopy loci were identified using a genome-wide association study approach but showed limited replication across several white populations. This study suggests that large-scale analyses with results from multiple populations will be needed to reliably identify key genetic factors underlying atopy predisposition. (J Allergy Clin Immunol 2011;127:223-31.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据