Susceptibility Genes for Allergic Rhinitis and Allergy
Susceptibility Genes for Allergic Rhinitis and Allergy
Although GWASs of allergic diseases have achieved great success in identifying genetic susceptibility loci, the identified variants have small effects with respect to the cause of diseases and explain little of the heritability. This 'missing heritability' phenomenon results from endophenotype confounding, unmapped common and rare variants, copy-number variations (CNV), epigenetic effects, gene–gene interactions and gene–environment interactions. For example, by defining the endotypes of asthma, one GWAS has recently identified a new locus, CDHR3, associated with childhood severe asthma with exacerbation. Additionally, exome sequencing and fine mapping of candidate loci via resequencing have discovered other important rare variants and CNV, which have biologic function.
Epigenetic modifications determine and mediate the environmental influences on gene expression, via the underlying epigenetic mechanisms which regulate the expression of key molecules or pathways in immunity related to the pathogenesis of allergic disorders. Thus, promoter methylation, histone tail modification and noncoding RNAs may become candidate targets for genetic associations.
As translation of the biology of identified genetic changes is currently a major difficulty, Encyclopaedia of DNA elements consortium (ENCODE) aims to identify the regulatory regions of the genome and expression of quantitative trait loci (eQTL) to provide further insight into the functional mechanisms.
Future Research
Although GWASs of allergic diseases have achieved great success in identifying genetic susceptibility loci, the identified variants have small effects with respect to the cause of diseases and explain little of the heritability. This 'missing heritability' phenomenon results from endophenotype confounding, unmapped common and rare variants, copy-number variations (CNV), epigenetic effects, gene–gene interactions and gene–environment interactions. For example, by defining the endotypes of asthma, one GWAS has recently identified a new locus, CDHR3, associated with childhood severe asthma with exacerbation. Additionally, exome sequencing and fine mapping of candidate loci via resequencing have discovered other important rare variants and CNV, which have biologic function.
Epigenetic modifications determine and mediate the environmental influences on gene expression, via the underlying epigenetic mechanisms which regulate the expression of key molecules or pathways in immunity related to the pathogenesis of allergic disorders. Thus, promoter methylation, histone tail modification and noncoding RNAs may become candidate targets for genetic associations.
As translation of the biology of identified genetic changes is currently a major difficulty, Encyclopaedia of DNA elements consortium (ENCODE) aims to identify the regulatory regions of the genome and expression of quantitative trait loci (eQTL) to provide further insight into the functional mechanisms.