Genomic Predictors of Asthma Phenotypes and Treatment Response

Abstract

Asthma is a complex respiratory disease considered as the most common chronic condition in children. A large genetic contribution to asthma susceptibility is predicted by the clustering of asthma and allergy symptoms among relatives and the large disease heritability estimated from twin studies, ranging from 55 to 90%. Genetic basis of asthma has been extensively investigated in the past 40 years using linkage analysis and candidate-gene association studies. However, the development of dense arrays for polymorphism genotyping has enabled the transition toward genome-wide association studies (GWAS), which have led the discovery of several unanticipated asthma genes in the last 11 years. Despite this, currently known risk variants identified using many thousand samples from distinct ethnicities only explain a small proportion of asthma heritability. This review examines the main findings of the last 2 years in genomic studies of asthma using GWAS and admixture mapping studies, as well as the direction of studies fostering integrative perspectives involving omics data. Additionally, we discuss the need for assessing the whole spectrum of genetic variation in association studies of asthma susceptibility, severity, and treatment response in order to further improve our knowledge of asthma genes and predictive biomarkers. Leveraging the individual's genetic information will allow a better understanding of asthma pathogenesis and will facilitate the transition toward a more precise diagnosis and treatment.

Recent findings in the genetics and epigenetics of asthma and allergy

“…To achieve this goal, the international consortium on Pharmacogenomics in Childhood Asthma (PiCA) was formed recently. Bringing together studies with GWAS data already available across different countries and ethnicities, this consortium was able to determine a handful of genetic risk factors for an insufficient response to inhaled corticosteroids (ICS) and exacerbations in children and young adults of Caucasian, Hispanic, and African American origin [72]. Especially, a locus on chromosome 22 harboring APOBEC3B and APOBEC3C was identified in admixed populations and was replicated in follow-up studies of European origin.…”

Understanding the genetics of asthma and implications for clinical practice

“…While there is no universal consensus, there appear to be approximately five to seven distinct groups, depending on source 11 . These have been broadly classified into two primary groups: atopic (eosinophilic) and non-atopic (non-eosinophilic) asthma, also commonly referred to as allergic/non-allergic or intrinsic/extrinsic asthma 5 . In this paper we adhere to "atopic" which infers that the host has a genetic tendency to produce eosinophils and IgE antibiodies in response to antigens which are surface markers found on the surface of allergens.…”

<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

“…12 The evidence of the role of genetic variants on asthma treatment response has been summarized in some recent reviews. [13][14][15][16][17][18] Thereby, this review aims to update the current findings described in pharmacogenetic studies of pediatric asthma published from 2018 through 2019.…”

“…Dijk et al56 also evaluated the role of a gene identified by previous GWAS of asthma,14,64 IL1RL1, on the response to ICS measured as asthma exacerbations (OCS use and Hospitalizations/ER visits).…”