Update on the genetics of allergic diseases

The field of genetic etiology of allergic diseases has advanced significantly in recent years. Shared risk loci reflect the contribution of genetic factors to the sequential development of allergic conditions across the atopic march, while unique risk loci provide opportunities to understand tissue specific manifestations of allergic disease. Most identified risk variants are noncoding, indicating that they likely influence gene expression through gene regulatory mechanisms. Despite recent advances, challenges persist, particularly regarding the need for increased ancestral diversity in research populations. Further, while polygenic risk scores show promise for identifying individuals at higher genetic risk for allergic diseases, their predictive accuracy varies across different ancestries and can be difficult to translate to an individual's absolute risk of developing a disease. Methodologies, including "nearest gene," 3D chromatin interaction analysis, expression quantitative trait locus analysis, experimental screens, and integrative bioinformatic models, have established connections between genetic variants and their regulatory targets, enhancing our understanding of disease risk and phenotypic variability. In this review, we focus on the state of knowledge of allergic sensitization and 5 allergic diseases: asthma, atopic dermatitis, allergic rhinitis, food allergy, and eosinophilic esophagitis. We summarize recent progress and highlight opportunities for advancing our understanding of their genetic etiology.