< 1 × 10−8 in either Fisher’s exact test or SAIGE SPA (Pearson’s r = 0.99) and Fisher’s exact test or REGENIE 2.0.2 (Pearson’s r = 0.99) (Supplementary Figs. 1, 2, Supplementary Table 6). The median lambda inflation factor λGC for the Fisher’s exact test was 1.0006 (range: 0.9675–1.0698) compared with a median λGC of 0.9953 (range: 0.9372–1.0940) for SAIGE SPA and a median λGC of 1.0001 (range: 0.9439–1.0602) for REGENIE 2.0.2 (Supplementary Table 7). Finally, we found that the Fisher’s exact test was the most computationally efficient of the three methods (Supplementary Table 6). In this setting, the Fisher’s exact test offered a statistically robust and efficient alternative to regression-based approaches, but required careful quality control, case–control harmonization and ancestry pruning before association testing.
