Genetic effects of multiple asthma loci identified by genomewide association studies on asthma and spirometric indices

Background Genomewide association study (GWAS) published by GABRIEL consortium identified 10 asthma‐associated loci. However, their relationship with lung functions is unclear. This study investigated the association between asthma traits and single‐nucleotide polymorphisms (SNPs) of these GWAS loci. Methods Rs3894194 and rs9273349 were not genotyped due to unavailable TaqMan assays. Genetic associations of remaining eight SNPs were investigated in 903 school‐age asthmatics and 1205 non‐allergic controls. Four significant SNPs were then replicated in 479 adult asthmatics and 746 adult controls, and 1341 Chinese preschool children. Meta‐analyses were performed by combining data from school‐age children and adults. Generalized multifactor dimensionality reduction (GMDR) was used to analyze their interactions for asthma traits. Results Childhood asthma was associated with GSDMB_rs2305480 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57–0.83). IL13_rs1295686 was associated with all asthma (OR 1.64, 95% CI 1.16–2.32) and early‐onset asthma (OR 1.92, 95% CI 1.20–3.06) in adults, whereas GSDMB_rs2305480 was only associated with early‐onset asthma (OR 0.69, 95% CI 0.49–0.96). According to meta‐analyses, the minor allele of rs2305480 was inversely associated with FEV1, FVC, and FEV1/FVC (p < 0.01). GMDR analyses revealed 2‐locus models of SLC22A5 with SMAD3 to modulate FEVt/FVC in both preschool children and adults, with IL13 to determine FVC in both school‐age children and adults, and with IL2RB to modulate FEV1/FVC in school‐age children. Conclusions IL13 and GSDMB are replicated as asthma genes. Rs2305480 of GSDMB is also associated with low FEV1, FVC, and FEV1/FVC among asthmatics. Moreover, SLC22A5, IL13, SMAD3, and GSDMB interact to modulate spirometric indices.