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. Author manuscript; available in PMC: 2018 May 3.
Published in final edited form as: Neuron. 2017 May 3;94(3):486–499.e9. doi: 10.1016/j.neuron.2017.04.024

Table 3.

Contribution of De Novo SNVs to TD Risk

Variant Type Theoretical rate per child (±95% CI)a % of cases with mutation mediating risk (±95% CI) % of mutations carrying risk (±95% CI)
Combined TD Cohort
TD Control
(N = 484) (N = 602)
Likely Gene Disrupting (LGD) 0.098 (0.067 – 0.13) 0.048 (0.028 – 0.067) 5.0% (1.3%–8.7%) 51.3% (13.7%–89.0%)
Damaging (LGD + Mis3) 0.51 (0.44 – 0.58) 0.39 (0.33 – 0.45) 11.6% (2.4%–20.8%) 22.9% (4.8%–41.0%)

To estimate the percentage of probands in whom a de novo variant is contributing to TD risk, we subtracted the theoretical rate, per exome, of de novo variants in controls from the theoretical rate in probands (Iossifov et al., 2014; Sanders et al., 2015). We predict that 5.0% (95% CI 1.3%–8.7%) of cases have a de novo LGD variant and 11.6% (95% CI 2.4%–20.8%) of cases have a de novo damaging variant contributing TD risk. To estimate the fraction of observed proband de novo variants that contribute to TD risk, we divided the difference in theoretical rate by the theoretical rate in probands (Iossifov et al., 2014; Sanders et al., 2015). Based on this approach, we predict that 51.3% (95% CI 13.7%–89.0%) of de novo LGD and 22.9% (95% CI 4.8%–41.0%) of de novo damaging variants carry TD risk.

a

Theoretical rate per child was calculated per individual. Mean theoretical rate and 95% CI was then calculated per cohort based on individual rates (see STAR Methods and Table 2 for more details)