Childhood-onset asthma is associated with the most independent loci compared with other defined groups of asthma and allergic disease cases, according to a review published in The Journal of Allergy and Clinical Immunology. Furthermore, adult-onset asthma and moderate-to-severe asthma are linked with fewer genes, which are largely a subset of those associated with childhood-onset asthma.
Researchers focused on genome-wide association studies (GWASs) of asthma and allergic diseases published between January 1, 2018 and June 30, 2019. During this period, there were 38 GWASs reported in 19 articles, including the largest performed to date for many of these conditions.
“There is significant genetic overlap between asthma and allergic diseases, particularly with respect to childhood-onset asthma, which involves genes that reflect the importance of barrier function biology, and to HLA region genes, which are the most frequently associated genes overall in both groups of diseases,” the study authors wrote. “Although the largest GWASs in Black and Latino/Hispanic populations were reported during this period, they are still significantly underpowered compared with studies reported in populations of European ancestry, highlighting the need for larger studies, particularly in patients with childhood-onset asthma and allergic diseases, in these important populations that carry the greatest burden of disease.”
Early-Onset Asthma Has Stronger Genetic Component than Adult-Onset Disease
The studies reviewed, according to researchers, both support and challenge the notion that “bigger is better.” “Clearly, the availability of very large data sets, such as the UK Biobank and large meta-analyses, have significantly advanced our knowledge of the genetic architecture of asthma and allergic diseases in European ancestry populations,” they wrote. “The data further demonstrates that early-onset asthma has a stronger genetic component and greater heritability than onset of asthma in adulthood, with more than 2.5 times the number of genome-wide significant loci associated with the former compared with the latter, despite at least double the sample sizes for the latter compared with the former.”
Similarly, the study team added, a relatively small study of asthmatic patients selected to have moderate-to-severe disease revealed more associated loci than larger studies of “asthma” in more heterogeneous populations. Finally, studies of highly specific food allergies (ie, hydrolyzed wheat protein, shrimp, peach, and peanut) in relatively small samples provided genome-wide significant associations with variants in the class II HLA region.
The researchers noted that many whole-genome sequencing studies are underway in both large cohorts and smaller but more homogenous and deeply phenotyped subjects, and the value of these studies should be revealed during the next few years. “Newer approaches, such as reverse phenotyping of subjects using genetic markers to define endotypes and integrating of multi-omics measures using machine learning and other advance computational tools, are already becoming standard,” they wrote. “Finally, there is still a need for fine-mapping studies at associated loci to pinpoint causal variants and the genes they regulate, as well as functional validation studies that link the effects of genetic risk and disease mechanisms to disease, which have been done thus far for surprisingly few asthma and allergic disease loci.”
