Background: Genome-wide association studies (GWAS) of childhood asthma have been revealed novel genes such as ORMDL3 and confirmed associations of previously reported genes. Butyrophilin-like 2 (BTNL2) is a member of the B7 receptor family known to play an important role in regulating T cell activation and tolerance. The association of the BTNL2 gene with childhood asthma has not been demonstrated yet. Objectives: We conducted GWAS of childhood asthma and focused on the association of genetic variants of BTNL2 associated with childhood asthma. Methods: Two hundred forty-three children with well-defined atopic asthma and 139 control subjects with a negative history of both allergic disease and allergic sensitization were enrolled. In all subjects, we have conducted genome-wide association study (GWAS) using AxiomTM Genome-Wide Array Plates (Affymetrix, CA, USA). Results: Single nucleotide polymorphisms (SNPs) at BTNL2 gene were most significantly associated with atopic asthma ( P = 6.29 x 10-7) even though it did not reach a genome-wide threshold of significance ( P 1.18 x 10-7). A total of 46 SNPs of BTNL2 gene on chromosome 6p were found. We observed associations of significance between atopic asthma and the following 4 SNPs after Bonferroni correction: rs3817971, rs41355746, rs41441651 and rs41499544. There were also 10 more associated SNPs with atopic asthma at nominal significance. Conclusions: We identified BTNL2 gene associated with atopic asthma in Korean children. BTNL2 would be added to the susceptible genes which need further investigations including functional research and network analysis in childhood asthma. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (NRF-2010-0025171).