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Background  Many studies have attempted to identify gene-gene interactions affecting asthma susceptibility. However, these studies have typically used candidate gene approaches in limiting the genetic search space, and there have been few searches for gene-gene interactions on a genome-wide scale. We aimed to conduct a genome-wide gene-gene interaction study for asthma, using data from the GABRIEL Consortium.    Results  A two-stage study design was used, including a screening analysis ( N  = 1625 subjects) and a follow-up analysis ( N  = 5264 subjects). In the screening analysis, all pairwise interactions among 301,547 SNPs were evaluated, encompassing a total of 4.55 × 10 10  interactions. Those with a screening interaction  p -value < 10 −5  were evaluated in the follow-up analysis. No interaction selected from the screening analysis met strict statistical significance in the follow-up ( p -value < 1.45 × 10 −7 ). However, the top-ranked interaction (rs910652 [20p13] × rs11684871 [2q14]) in the follow-up ( p -value = 1.58 × 10 −6 ) was significant in one component of a replication analysis. This interaction was notable in that rs910652 is located within 78 kilobases of  ADAM33 , which is one of the most well studied asthma susceptibility genes. In addition, rs11684871 is located in or near  GLI2 , which may have biologically relevant roles in asthma.    Conclusions  Using a genome-wide approach, we identified and found suggestive evidence of replication for a gene-gene interaction in asthma involving loci that are potentially highly relevant in asthma pathogenesis.    Electronic supplementary material  The online version of this article (doi:10.1186/s12863-016-0376-3) contains supplementary material, which is available to authorized users.

Genome-wide search identifies a gene-gene interaction between 20p13 and 2q14 in asthma