Advances in asthma and allergic disease genetics.

Abstract

Asthma and allergic disease are common chronic conditions affecting individuals of all ages. The contribution of genetics to the risk of asthma and allergic diseases is well established, yet the mechanisms through which genetic variation contribute to risk continues to be investigated. This review focuses on recent advances made in genetic studies of asthma and allergic disease phenotypes. Progress has been made at expanding genetic studies of asthma and allergic diseases in more diverse and non-European populations, and genetic associations have been made with loci and more refined phenotypes associated with these conditions. Among the 11 large genome-wide association studies or admixture mapping studies published recently, 52 novel associations were identified for asthma and allergic disease phenotypes. As in previous studies, variant- and genome-based heritability remains relatively low. The use of polygenic risk scores in asthma and allergic diseases has increased and reinforces the remarkable overlap of the genetic risk of these conditions. Whole genome and exome sequencing has led to associations of specific genes with these conditions, including rare STAT6 gain-of-function mutations that were identified in individuals with multiple, severe and early life allergic diseases and asthma. Overall, we have learned that asthma and allergic diseases phenotypes are highly polygenic and have considerable overlap in their genetic landscapes.