There is a male:female sex bias in both the TIC Genetics (3.64; Table 1) and TSAICG (4.97) cohorts but not in the SSC sibling trios (0.84); however, mutation rates were not significantly different between males and females in the TIC Genetics (p = 0.4, two-sided rate ratio test; Table S1), TSAICG (p = 0.9), or SSC siblings (p = 0.3) cohorts. Therefore, despite the differences in sex ratio, the direction of effect suggests that, if anything, there is a slightly higher rate of de novo variants in females, and therefore, a male-biased TD cohort and a non-male-biased control cohort should result in conservative burden estimates.
