Finally, we evaluated time and memory complexity for linear mixed model analyses of 2504 individuals—a unique feature of RVTESTS. The analyses using single variant, simple burden, SKAT and VT tests took 17/19/1514/856 CPU hours. On a workstation with 64 GB RAM, our tool can handle datasets with 64 000 genotyped individuals. Given that the LMM analyses have linear complexity with respect to the number of genes and quadratic complexity with respect to the number of samples (after spectral decompositions), it is clear that RVTESTS can handle large datasets genotyped on tens of millions of markers (Supplementary Table S4).
