A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD

Ah Ra Do; Jin An; Jinyeon Jo; Woo Jin Kim; Hae Yeon Kang; Sanghun Lee; Dankyu Yoon; You Sook Cho; Ian M Adcock; Kian Fan Chung; Sungho Won; Tae-Bum Kim

doi:10.1038/s41598-022-24766-6

A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD

Sci Rep. 2022 Dec 21;12(1):22073. doi: 10.1038/s41598-022-24766-6.

Authors

Ah Ra Do^#¹, Jin An^#², Jinyeon Jo³, Woo Jin Kim⁴, Hae Yeon Kang⁵, Sanghun Lee⁶, Dankyu Yoon⁷, You Sook Cho⁸, Ian M Adcock⁹, Kian Fan Chung⁹, Sungho Won^#^{10

11

12

13}, Tae-Bum Kim^#^{14

15}

Affiliations

¹ Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, South Korea.
² Department of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, South Korea.
³ Department of Public Health Sciences, School of Public Health, Seoul National University, Kwanak-ro 1, Kwanak-gu, Seoul, 151-742, Korea.
⁴ Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, South Korea.
⁵ Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
⁶ Deptartment of Medical Consilience, Division of Medicine, Graduate School, Dankook University, Yongin, South Korea.
⁷ Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Korea.
⁸ Department of Internal Medicine, Division of Allergy and Clinical Immunology, Asan Medical Center, Ulsan University School of Medicine, Seoul, South Korea.
⁹ Experimental Studies, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
¹⁰ Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, South Korea. sunghow@gmail.com.
¹¹ Department of Public Health Sciences, School of Public Health, Seoul National University, Kwanak-ro 1, Kwanak-gu, Seoul, 151-742, Korea. sunghow@gmail.com.
¹² Institute of Health and Environment, Seoul National University, Seoul, South Korea. sunghow@gmail.com.
¹³ RexSoft Inc., Seoul, Korea. sunghow@gmail.com.
¹⁴ Department of Internal Medicine, Division of Allergy and Clinical Immunology, Asan Medical Center, Ulsan University School of Medicine, Seoul, South Korea. tbkim@amc.seoul.kr.
¹⁵ Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, 138-736, Korea. tbkim@amc.seoul.kr.

^# Contributed equally.

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ([Formula: see text] = 0.44, P-value_Asthma-COPD = 3.41 × 10^-8), and significant results were replicated with the UK Biobank data ([Formula: see text] = 0.04, P-value_Asthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40-45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study / methods
Humans
Inflammation
Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive* / genetics

Abstract

Publication types

MeSH terms

Grants and funding