Genetics of allergy and allergic sensitization: common variants, rare mutations

• Published in: Current opinion in immunology Vol. 36; pp. 115 - 126
• Main Authors: Bønnelykke, Klaus, Sparks, Rachel, Waage, Johannes, Milner, Joshua D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2015
• Subjects: Allergy and Immunology; Animals; Autoimmunity - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Hypersensitivity - genetics; Hypersensitivity - immunology; Immunization; Mutation; Phenotype; Quantitative Trait Loci; Quantitative Trait, Heritable
• ISSN: 0952-7915; 1879-0372; 1879-0372
• DOI: 10.1016/j.coi.2015.08.002

•GWAS have identified robust allergy loci involving immune and yet unknown mechanisms.•Comparing loci between allergy phenotypes suggest differential and shared mechanisms.•Monogenic diseases with atopic features also reveal novel pathways.•Shared genetics for allergy and autoimmunity suggest common disease pathways. Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T-cell differentiation, TGFβ signaling, regulatory T-cell function and skin/mucosal function as well as yet unknown mechanisms associated with newly identified genes. Future studies, in combination with data on gene expression and epigenetics, are expected to increase our understanding of the pathogenesis of allergy.