Study identifies genetic variations linked to allergic sensitization

Humans are continuously exposed to various environmental allergens (antigens), such as pollen, food, and dust mites. In certain individuals, their immune system recognizes common environmental antigens as foreign substances, resulting in the production of allergy-related antibodies known as immunoglobulin E (IgE). This condition, wherein IgE antibodies specific to common environmental allergens are produced in the human body, is called allergic sensitization. Because sensitization usually precedes the clinical manifestation of allergic diseases, it is an important marker for evaluating such conditions and exploring preventive strategies.

The research team performed a genome-wide association study (GWAS) using genotype data on 46,602 Japanese individuals collected by the University of Tsukuba and Tohoku Medical Megabank. By conducting a comprehensive analysis, the team examined the association between genetic polymorphisms-inter-individual genetic variations-and the status of allergic sensitization. They then integrated these findings with GWAS data on a European population of 25,032 individuals to identify genetic polymorphisms related to allergic sensitization.

The research team found 18 Japanese-specific genetic polymorphisms associated with sensitization and 23 genetic polymorphisms detected through the meta-analysis of both Japanese and European datasets. Moreover, the team performed the first GWAS on polysensitization (sensitization to multiple allergens), identifying eight associated genetic polymorphisms.

Subsequent detailed analyses revealed that the genetic predisposition to allergic sensitization exerts a weaker influence on the onset of atopic dermatitis compared with asthma, allergic rhinitis, and pollinosis. These findings represent a major advancement in elucidating the underlying molecular mechanisms of allergic diseases, potentially contributing to the development of novel preventive and therapeutic strategies.

This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS, nos. 21J11802 and 23H03143), a Grant-in-Aid for JSPS Fellows, and by the Japan Agency for Medical Research and Development (AMED, nos JP20ek0410076 and JP21tm0424601).