Replication of genome-wide association study loci for allergic rhinitis and house dust mite sensitization in an Asian population of ethnic Chinese in Singapore

Andiappan, Anand Kumar; Wang, De Yun; Anantharaman, Ramani; Suri, Bani Kaur; Lee, Bernett Teck Kwong; Rötzschke, Olaf; Li, Jianjun; Chew, Fook Tim

doi:10.1016/j.jaci.2012.11.001

Cited by 12 publications

(14 citation statements)

References 12 publications

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“…A limitation of traditional genome-wide association studies is that statistically significant loci may be identified [4,9], but the biological relevance of the individual or aggregate variants are often not evident [11,12]. This is not overcome by replication of genotype associations, which has been the usual path taken to follow up GWAS findings, and one which has led to limited success [7,9,41]. Our study demonstrates the advantages of integrating network approaches with GWAS to identify and prioritize pathways and gene targets of biologic relevance.…”

Section: Discussionmentioning

confidence: 99%

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis

et al. 2014

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BackgroundAllergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.MethodsWe performed genome wide association studies (GWAS) of allergic rhinitis in 5633 ethnically diverse North American subjects. Next, we profiled gene expression in disease-relevant tissue (peripheral blood CD4+ lymphocytes) collected from subjects who had been genotyped. We then integrated the GWAS and gene expression data using expression single nucleotide (eSNP), coexpression network, and pathway approaches to identify the biologic relevance of our GWAS.ResultsGWAS revealed ethnicity-specific findings, with 4 genome-wide significant loci among Latinos and 1 genome-wide significant locus in the GWAS meta-analysis across ethnic groups. To identify biologic context for these results, we constructed a coexpression network to define modules of genes with similar patterns of CD4+ gene expression (coexpression modules) that could serve as constructs of broader gene expression. 6 of the 22 GWAS loci with P-value ≤ 1x10−6 tagged one particular coexpression module (4.0-fold enrichment, P-value 0.0029), and this module also had the greatest enrichment (3.4-fold enrichment, P-value 2.6 × 10−24) for allergic rhinitis-associated eSNPs (genetic variants associated with both gene expression and allergic rhinitis). The integrated GWAS, coexpression network, and eSNP results therefore supported this coexpression module as an allergic rhinitis module. Pathway analysis revealed that the module was enriched for mitochondrial pathways (8.6-fold enrichment, P-value 4.5 × 10−72).ConclusionsOur results highlight mitochondrial pathways as a target for further investigation of allergic rhinitis mechanism and treatment. Our integrated approach can be applied to provide biologic context for GWAS of other diseases.

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Section: Discussionmentioning

confidence: 99%

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis

et al. 2014

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“…The associations detected by GWAS include the protein kinase domain containing, cytoplasmic (PKDCC) with allergen sensitization in Europeans [73]; thymic stromal lymphopoietin (TSLP) and leucine rich repeat containing 32 (LRRC32) with sensitization to D. pteronyssinus and B. tropicalis in Singapore (ethnic Chinese) [75]. There are still regions to be fine-mapped because the underlying genes in the associated loci are unknown.…”

Section: Genetics Of Ige Responses To Mite Allergensmentioning

confidence: 99%

International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem

Sánchez‐Borges

Fernández-Caldas

Thomas

et al. 2017

World Allergy Organization Journal

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Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.

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“…Cytokines and immunity related pathways, such as cytokine production, Th17 cell differential and regulation of cytokine secretion, were significantly enriched and shared among GWASs (Additional file 1: Figure S1). However, few of studies have been convincingly and highly replicated especially in Chinese [5,16]. The aim of the present study is to investigate the highly replicated allergy related genes and variants as candidates for AR in Han Chinese.…”

Section: Introductionmentioning

confidence: 96%

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

Gao

Zhang

et al. 2020

Allergy Asthma Clin Immunol

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Background: Allergic rhinitis (AR) is believed to be a complex genetic disease. The last decade has been marked by the publication of more than 20 genome-wide association studies (GWASs) of AR and associated allergic phenotypes and allergic diseases, which have shown allergic diseases and traits to share a large number of genetic susceptibility loci. The aim of present study was therefore to investigate the highly replicated allergy related genes and variants as candidates for AR in Han Chinese subjects. Methods: A total of 762 AR patients and 760 control subjects were recruited, and a total of 58 susceptible variants previously reported to be associated with allergic traits were choose for replication. Results: Logistic regression analyses revealed that in the co-dominant-effect model as assessed by the AIC, compared with wild-type carriers, significant AR risk were associated with rs9865818 in LPP (P = 0.029, OR = 1.469 for GG vs. AA); rs6554809 in DNAH5 (P = 0.000, OR = 1.597 for TC vs. CC); rs1438673 in WDR36-CAMK4 loci (P = 0.037, OR = 1.396 for CC vs.TT), rs7775228 in HLA region (P = 0.000, OR = 1.589 for TC vs.TT), rs7203459 in CLEC16A (P = 0.025, OR = 0.731 for TC vs. TT). Conclusion: We replicated Han Chinese AR-specific susceptibility loci in LPP, DNAH5, HLA, CLEC16A and WDR36-CAMK4. Further understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

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Replication of genome-wide association study loci for allergic rhinitis and house dust mite sensitization in an Asian population of ethnic Chinese in Singapore

Cited by 12 publications

References 12 publications

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis

International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

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