AbstractA genome‐wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood‐onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood‐onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12–1.65, P = 0.002] and an OR of 1.36 (95% CI 1.07–1.74, P = 0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR = 1.57, 95% CI 1.04–2.36, P = 0.032; recessive OR = 1.41, 95% CI 1.09–1.83, P = 0.009; additive OR = 1.97, 95% CI 1.24–3.14, P = 0.004; recessive OR = 1.50, 95% CI 1.13–1.98, P = 0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10‐transformed immunoglobulin E (IgE) level (IU/ml) and log10‐transformed eosinophil percentage (dominant, P = 0.04; additive, P = 0.01; recessive, P = 0.04; recessive, P = 0.03; additive, P = 0.02). Collectively, our findings suggest that orosomucoid 1‐like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood‐onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood‐onset asthma.