was not a significant predictor (Table S1). After controlling for these additional covariates in the Poisson multiple regression, de novo LGD variants still remained significantly associated with TD risk (Figure 4; RR 2.20, 95% CI 1.19–4.08, p = 0.01; RR 2.23, 95% CI 1.04–4.82, p = 0.04 in TIC Genetics and TSAICG, respectively). Additionally, de novo damaging variants (LGD + Mis3) showed enrichment in the TIC Genetics cohort (RR 1.38, 95% CI 1.08–1.76, p = 0.009) and a trend toward enrichment in the TSAICG cohort (RR 1.37, 95% CI 0.98–1.92, p = 0.07). Mis3 variants alone were no longer significantly associated in either cohort, although we still observed evidence of modest effects in the TIC Genetics (RR 1.27, 95% CI 0.97–1.65, p = 0.08) cohort.
