Motivation: Several efficient gene–gene interaction tests have been developed for unrelated case–control samples in genome-wide association studies (GWAS), making it possible to test tens of billions of interaction pairs of single-nucleotide polymorphisms (SNPs) in a reasonable timeframe. However, current family-based gene–gene interaction tests are computationally expensive and are not applicable to genome-wide interaction analysis.

Results: We developed an efficient family-based gene–gene interaction test, GCORE, for trios (i.e. two parents and one affected sib). The GCORE compares interlocus correlations at two SNPs between the transmitted and non-transmitted alleles. We used simulation studies to compare the statistical properties such as type I error rates and power for the GCORE with several other family-based interaction tests under various scenarios. We applied the GCORE to a family-based GWAS for autism consisting of approximately 2000 trios. Testing a total of 22 471 383 013 interaction pairs in the GWAS can be finished in 36 h by the GCORE without large-scale computing resources, demonstrating that the test is practical for genome-wide gene–gene interaction analysis in trios.

Availability and implementation: GCORE is implemented with C ++ and is available at

Contact:  [email protected]

Supplementary information:  Supplementary data are available at Bioinformatics online.