Poor Reproducibility of Allergic Rhinitis SNP Associations

10.1371/journal.pone.0053975PLoS ONE81

Evaluation of the applicability of the Immuno-solid-phase allergen chip (ISAC) assay in atopic patients in Singapore

BACKGROUND/OBJECTIVE: Molecular-based allergy diagnostics are gaining popularity in clinical practice. Our aim was to evaluate their role in the tropics, given the inherent genetic and environmental differences. METHODS: We recruited subjects with history of atopy and collected data on demographics and atopic symptoms using validated questionnaires. Subjects underwent a series of skin prick tests (SPT). Serum total and specific IgE levels were measured using ImmunoCAP FEIA and ImmunoCAP ISAC®, respectively. We describe their pattern of sensitization and agreement between test methods. RESULTS: A total of 135 subjects were recruited; mean ± SD age of 31.18 ± 12.72 years, 52.7% female. Allergic rhinitis (AR) was the most prevalent clinical manifestation of atopy (70.7%), followed by atopic dermatitis (AD) (50.5%) and asthma (26.2%). Polysensitization was seen in 51.1% of subjects by both SPT and ISAC. House dust mites (HDM) were the dominant allergen, with sensitization in 67.8% and 62% of subjects on SPT and ISAC, respectively. A group of subjects with monosensitization to B. tropicalis was identified. HDM sensitization was strongly associated with AR, while AD and asthma were not associated with sensitization to any allergen. Agreement between SPT and ISAC was mostly suboptimal. Greatest agreement was documented for the measurement of HDM sensitization with both methods (κ = 0.64). Sensitization to the bulk of the remaining allergens in the ISAC panel was infrequent. CONCLUSION: Multiplex methods should not be used as a screening tool, especially in a population with lower rates of polysensitization and a dominant sensitizing allergen. There may be a role in adjusting the antigen spectrum in the ISAC panel to regional differences. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13601-015-0053-z) contains supplementary material, which is available to authorized users

Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with Allergic Rhinitis in Singapore Chinese

<p>Abstract</p> <p>Background</p> <p>Uteroglobin-Related Protein 1 (<it>UGRP1</it>) is a secretoglobulin protein which has been suggested to play a role in lung inflammation and allergic diseases. UGRP1 has also been shown to be an important pneumoprotein, with diagnostic potential as a biomarker of lung damage. Previous genetic studies evaluating the association between variations on <it>UGRP1 </it>and allergic phenotypes have yielded mixed results. The aim of this present study was to identify genetic polymorphisms in <it>UGRP1 </it>and investigate if they were associated with asthma and allergic rhinitis in the Singapore Chinese population.</p> <p>Methods</p> <p>Resequencing of the <it>UGRP1 </it>gene was conducted on 40 randomly selected individuals from Singapore of ethnic Chinese origin. The polymorphisms identified were then tagged and genotyped in a population of 1893 Singapore Chinese individuals. Genetic associations were evaluated in this population comparing 795 individuals with allergic rhinitis, 718 with asthma (of which 337 had both asthma and allergic rhinitis) and 717 healthy controls with no history of allergy or allergic diseases.</p> <p>Results</p> <p>By resequencing the <it>UGRP1 </it>gene within our population, we identified 11 novel and 16 known single nucleotide polymorphisms (SNPs). TagSNPs were then genotyped, revealing a significant association between rs7726552 and allergic rhinitis (Odds Ratio: 0.81, 95% Confidence Interval: 0.66-0.98, P = 0.039). This association remained statistically significant when it was analyzed genotypically or when stratified according to haplotypes. When variations on <it>UGRP1 </it>were evaluated against asthma, no association was observed.</p> <p>Conclusion</p> <p>This study documents the association between polymorphisms in <it>UGRP1 </it>and allergic rhinitis, suggesting a potential role in its pathogenesis.</p

Genome-wide association study identifies PERLD1 as asthma candidate gene

10.1186/1471-2350-12-170BMC Medical Genetics12-BMGM

Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances

We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify and replicate novel findings near ABO, ZC3HC1, and IGF2R. We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.Peer reviewe

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants

Cell Specific eQTL Analysis without Sorting Cells

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus