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 2,000 trios. Testing a total of 22,471,383,013 interaction pairs in the GWAS can be finished in 36 hours by the GCORE without large-scale computing resources, demonstrating that the test is practical for genome-wide gene-gene interaction analysis in trios.
