A genome-wide meta-analysis reveals shared and population-specific variants for allergic sensitization.

Background: Allergic diseases are major causes of morbidity in both developed and developing countries and represent a global burden on health care systems. Allergic sensitization is defined as the production of immunoglobulin E (IgE) specific to common environmental allergens, and it is an important indicator in the assessment of allergic diseases.

Objectives: This study aimed to clarify the genetic basis of allergic sensitization.

Methods: We performed a genome-wide association study (GWAS) of allergic sensitization in the Japanese population, followed by a cross-ancestry meta-analysis with a European population, involving a total of 20,492 cases and 23,342 controls for Japanese and 8,246 cases and 16,786 controls for Europeans. We also performed a polysensitization GWAS of a Japanese population involving 4,923 cases and 17,009 controls.

Results: A total of 18 susceptibility loci for Japanese only and 23 allergic sensitization loci for the cross-ancestry population were identified by GWAS, among which 4 loci were novel. We also identified 8 GWAS significant loci for polysensitization. Expression quantitative trait locus colocalization analysis revealed polysensitization GWAS significant variants affecting both the phenotype and expression of the CD28, LPP, and LRCC32 genes. Cross-population genetic correlation analysis of allergic sensitization suggested that heterogeneity exists in allergic sensitization between Europeans and Japanese, indicating that more genetic heterogeneity may exist in allergic sensitization than allergic diseases.

Conclusions: Our investigation provided new insights into the molecular mechanism of allergic sensitization that could enhance current understanding of allergy and allergic diseases.