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

Abstract

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. The main aim of this study was to identify single nucleotide polymorphisms (SNPs) with a pleiotropic effect on both asthma and COPD, and to evaluate the similarities between their genetic underpinnings. We performed a genome-wide association study (GWAS) of asthma and COPD in 7,828 Koreans from three hospitals and 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 (βAsthma-COPD = 0.44, P-valueAsthma-COPD = 3.41 × 10-8), and significant results were replicated with the UK Biobank data (βAsthma-COPD=0.04, P-valueAsthma-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. 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.