A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations

Wataru Morii; Koki Kasai; Takako Nakamura; Daisuke Hayashi; Monami Hara; Tatsuhiko Naito; Kyuto Sonehara; Tatsuki Fukuie; Mayako Saito-Abe; Limin Yang; Kiwako Yamamoto-Hanada; Masami Narita; Kazushi Maruo; Yukinori Okada; Emiko Noguchi; Yukihiro Ohya

doi:10.1016/j.jacig.2023.100086

A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations

J Allergy Clin Immunol Glob. 2023 Feb 20;2(2):100086. doi: 10.1016/j.jacig.2023.100086. eCollection 2023 May.

Authors

Wataru Morii¹, Koki Kasai¹, Takako Nakamura¹, Daisuke Hayashi¹, Monami Hara¹, Tatsuhiko Naito^{2

3

4}, Kyuto Sonehara^{2

5}, Tatsuki Fukuie⁶, Mayako Saito-Abe⁶, Limin Yang⁶, Kiwako Yamamoto-Hanada⁶, Masami Narita^{6

7}, Kazushi Maruo⁸, Yukinori Okada^{2

4

5

9

10}, Emiko Noguchi¹, Yukihiro Ohya⁶

Affiliations

¹ Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
² Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
³ Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁵ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
⁶ Allergy Center, National Center for Child Health and Development, Tokyo, Japan.
⁷ Department of Pediatrics, School of Medicine, Kyorin University, Tokyo, Japan.
⁸ Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
⁹ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
¹⁰ Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Japan.

Abstract

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed.

Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components.

Methods: The participants of the present study were recruited from the Tokyo Children's Health, Illness, and Development study, and allergen component-specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16).

Results: We performed GWAS on 564 participants of the Tokyo Children's Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10^-8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10^-8).

Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Keywords: Genome-wide association study; HLA; IGHV; allergen components; immunogenetics.