Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics

Jin An; Ah Ra Do; Hae Yeon Kang; Woo Jin Kim; Sanghun Lee; Ji Hyang Lee; Woo Jung Song; Hyouk Soo Kwon; You Sook Cho; Hee Bom Moon; Sile Hu; Ian M Adcock; Kian Fan Chung; Sungho Won; Tae Bum Kim

doi:10.4168/aair.2021.13.4.609

Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics

Allergy Asthma Immunol Res. 2021 Jul;13(4):609-622. doi: 10.4168/aair.2021.13.4.609.

Authors

Jin An^#^{1

2}, Ah Ra Do^#³, Hae Yeon Kang⁴, Woo Jin Kim⁵, Sanghun Lee⁶, Ji Hyang Lee¹, Woo Jung Song¹, Hyouk Soo Kwon¹, You Sook Cho¹, Hee Bom Moon¹, Sile Hu⁷, Ian M Adcock⁷, Kian Fan Chung⁷, Sungho Won^{3

8

9}, Tae Bum Kim¹⁰

Affiliations

¹ Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
² Department of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea.
³ Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Korea.
⁴ Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
⁵ Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Korea.
⁶ Department of Medical Consilience, Graduate School, Dankook university, Yongin, Korea.
⁷ Experimental Studies, Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, United Kingdom.
⁸ Department of Public Health Sciences, School of Public Health, Seoul National University, Seoul, Korea.
⁹ Institute of Health and Environment, Seoul National University, Seoul, Korea. sunghow@gmail.com.
¹⁰ Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. tbkim@amc.seoul.kr.

^# Contributed equally.

Abstract

Purpose: Although genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank.

Methods: Patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a P value of < 5 × 10^-8 was considered significant. We compared significant SNPs between Korean and UK patients with asthma.

Results: A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P = 4.5 × 10^-10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood.

Conclusions: The SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.

Keywords: Genome-wide association study; Korea; United Kingdom; asthma; genetics; human leukocyte antigen.

Abstract

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