Genome wide association studies (GWAS) performed for the lung function utilizing two strategically established adult cohort populations in Japan identified the AGER locus at 6p21.32 including exonic nonsynonymous SNP rs2070600 in AGER as the locus most significantly associated with FEV1/FVC, an important measure of pulmonary function. This was the first large-scale GWAS study for lung function in the Japanese population. While this locus was nicely replicated in the validation stage, the 3D structure-based assessment suggested that the SNP in AGER introduces a G82S substitution into one of the immunoglobulin domains in AGER, which likely affects the molecular function of the receptor. 

Based on the relationship between common variants in GWAS and rare variants in the genome reference panel, the researchers also performed an extensive search of their genomic allele reference panel, 4.7KJPN, and identified three rare missense variants of AGER. They also performed GWAS for FeNO and identified three genetic loci associated with the FeNO levels in the adult populations. The proteins encoded by the candidate genes in the loci are iNOS, SPSB2, and RIPOR2, which have functions that influence the levels of FeNO. This study provides an insight into the understanding of the pathogenesis of respiratory diseases including COPD and airway type 2 inflammation.