Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy (original) (raw)
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Medicine, 2018
Previous genetic studies of food allergy (FA) have mainly focused on inherited genotypic effects. The role of parental genotypic effects remains largely unexplored. Leveraging existing genome-wide association study (GWAS) data generated from the Chicago Food Allergy Study, we examined maternal genotypic and parent-of-origin (PO) effects using multinomial likelihood ratio tests in 588 complete and incomplete Caucasian FA trios. We identified 1 single nucleotide polymorphism with significant (P < 5×10) maternal effect on any FA (rs4235235), which is located in a noncoding RNA (LOC101927947) with unknown function. We also identified 3 suggestive (P < 5×10) loci with maternal genetic effects: 1 for any FA (rs976078, in a gene desert region on 13q31.1) and 2 for egg allergy (rs1343795 and rs4572450, in the ZNF652 gene, where genetic variants have been associated with atopic dermatitis). Three suggestive loci with PO effect were observed: 1 for peanut allergy (rs4896888 in the ADGB ...
Genetic aspects of food allergy
2011
The increasing prevalence of food allergy is a growing problem. This review examines recent developments in the genetic factors of food allergy. The use of genomic information, accelerated by the sequencing of the human genome and the advent of new tools and technologies, has raised widespread hope that food allergy genetics can significantly contribute to the prediction, prevention, and treatment of food allergy.
Review Paper Genetic aspects of food allergy
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 2011
The increasing prevalence of food allergy is a growing problem. This review examines recent developments in the genetic factors of food allergy. The use of genomic information, accelerated by the sequencing of the human genome and the advent of new tools and technologies, has raised widespread hope that food allergy genetics can significantly contribute to the prediction, prevention, and treatment of food allergy.
Environmental Toxicology and Pharmacology, 1997
Genetics of human diseases has passed through three main historical phases: (1) studies of formal genetics aimed at investigating mechanisms of inheritance using Mendelian models in population, family and twin surveys; (2) studies of associations between HLA antigens and diseases; and (3) direct mapping of genes through candidate gene or random genomic search approach. Very few data in each of these three phases are available for food allergy and intolerance. They are mostly confined to formal genetics studies of allergy in general and to HLA association studies in celiac diseases. The main reason for paucity of data in this important area of investigation is represented by the heterogeneity of the clinical entities grouped under the label of food allergy at the level of: (1) the clinical phenotype, because of the many diseases and end-organs interested; (2) pathophysiological variables involved, since several immunological and non-immunological mechanisms can be invoked in different cases of food allergy and intolerance; and (3) the foods or their absorbed metabolites which induce symptoms. However, progress made in genetics of allergy can be in part extrapolated to the limited number of cases where an IgE-mediated mechanism has been demonstrated. The review of studies based on a more punctual definition of the allergic phenotype and of the candidate genes (regions) of allergy: (1) suggests that allergen recognition and specific IgE response, total IgE (and IgG4) polyclonal activation, up-regulation of inflammatory cells (mast cells and eosinophils mainly) and hyper-responsiveness of end-organs are possibly regulated by different genetic and environmental factors; and (2) calls particular attention on the following genomic regions: 5q 31.1-33, 6p 21.3, 11q 13, 14. Research on genetics of food allergy and intolerance is highly recommended because of its high prevalence and of the potential applicative value of results for preventive measures of dietary control in subjects at risk. Since 'food allergy and intolerance' does not represent an useful phenotype for genetic studies because of its heterogeneity, adequate strategies of gene mapping should be designed in study groups selected for defined variables with a well established role in the pathogenesis of the different clinical expressions of this common condition.
Clinical & Experimental Allergy, 2017
Background: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genome-wide association study (GWAS) has been published. Objective: To identify genetic variants associated with challenge proven peanut allergy. Methods: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphism (SNPs), as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. Results: We identified 21 independent associations at P ≤ 5x10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2x10-4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. Conclusions & Clinical Relevance: Genetic determinants for challenge proven peanut allergy include alleles at the HLA-DRB1 locus.
A genome-wide association study for different types allergic diseases
International journal of biology and chemistry, 2022
All over the world, there is an active search for genes that are responsible for the formation of predisposition to allergic diseases, which is associated both with the undoubted relevance of studying risk factors for the development of allergies, and with the emergence of new opportunities for genetic research. In addition, anthropogenic impact can cause allergic reactions and modifications in the functions of antioxidant defense cells and the immune system. Due to the fact that in the cohort of the population of Almaty and the Almaty region (going forward we will say Almaty to include the region also), respiratory diseases with an allergic component, such as bronchial asthma, bronchitis, allergic rhinitis, are common, we consider it is appropriate to conduct an epidemiological study of candidate genes for allergic diseases-cytokines and their receptors (IL4, IL4RA , IL12B, IL13, TNFA, CCL5), adrenoreceptor (ADRB2), transcription factors involved in T-lymphocyte differentiation (STAT6, GATA3, TBX21), major histocompatibility complex (HLA-DRB1, HLA-DQB1). The aim of our study is to conduct genome-wide genotyping in people with allergic diseases and to search for marker genes that affect the risk of developing allergies as well as to identify genes that are involved in the pathogenesis of allergic diseases. We performed genome-wide microarray genotyping of 25355 SNPs on the iScan platform of 103 samples with allergic diseases and 108 control DNA samples using the kit (Infinium® ImmunoArray24-v2.0 BeadChip Kit). The results obtained, using the GWAS analysis, which considers numerous polymorphisms, showed the involvement of some genes in the development of allergic diseases (rs20541-asthma, allergic rhinitis, rs841718-atopic dermatitis, rs3212227-immunodeficiency).
Are genetic tests informative in predicting food allergy?
Current opinion in allergy and clinical immunology, 2016
Food allergy is common among children and adults worldwide. Recent studies have improved our understanding of the genetic mechanism of food allergy and further studies may result in clinical application through genetic testing. Genetic factors are important in the development of food allergy. An increasing number of genes have been associated with food allergy in recent years. These include mutations and variant in the filaggrin gene, the association of human leukocyte antigen DR and DQ regions with food allergy, copy number variation impacting CTNNA3 and RBFOX1, DNA methylation that partially mediates single nucleotide polymorphism association at the HLA-DR and DQ loci, as well as other genes. Several studies have implicated differences in gut microbiota composition in food allergy. With the advance of high-throughput genotyping and sequencing techniques together with improved analytical methods, the contributions of genetic and environmental factors in development of food allergy ...
HLA Polymorphisms and Food Allergy Predisposition
Journal of Pediatric Genetics, 2020
Food allergy (FA) is a growing health problem that affects ∼8% of the children worldwide. Although the prevalence of FA is increasing, the underlying genetic mechanisms responsible for the onset of this immune disorder are not yet clarified. Genetic factors seem to play a leading role in the development of FA, though interaction with environmental factors cannot be excluded. The broader network of genetic loci mediating the risk of this complex disorder remains to be identified. The human leucocyte antigen (HLA) has been associated with various immune disorders, including FA. This review aims to unravel the potential associations between HLA gene functions and the manifestation and outcome of FA disorders. Exploring new aspects of FA development with the perspective to improve our understanding of the multifaceted etiology and the complex biological mechanisms involved in FA is essential.
Nature communications, 2015
Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10(-8)) and rs9275596 (P=6.8 × 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites…