Table 2 characteristics of the models showing significant prediction in the testing sample for the phenotype TRD vs. response.

Subsample	Genetic predictors only	Genetic predictors + clinical risk score	Extreme genetic percentiles^a, genetic predictors only	Extreme genetic percentiles^a, genetic predictors + clinical score
(A) Pathway-based scores including rare variants
Whole testing set	AUC 0.61 (0.54–0.69) Sens = 0.42; spec = 0.77; PPV = 0.76; NPV = 0.43	AUC 0.73 (0.66–0.79) Sens = 0.79; spec = 0.57; PPV = 0.76; NPV = 0.60	AUC 0.66 (0.56–0.75) Sens = 0.53; spec = 0.76; PPV = 0.78; NPV = 0.51	AUC 0.75 (0.67–0.83) Sens = 0.79; spec = 0.60; PPV = 0.76; NPV = 0.65
5-HT drugs only	AUC 0.62 (0.52–0.73) Sens = 0.48; spec = 0.77; PPV = 0.76; NPV = 0.49	AUC 0.65 (0.55–0.76) Sens = 0.73; spec = 0.53; PPV = 0.70; NPV = 0.57	AUC 0.60 (0.45–0.74)	AUC 0.68 (0.55–0.82) Sens = 0.75; spec = 0.61; PPV = 0.75; NPV = 0.61
(B) Gene-based scores including common and rare vairants
Whole testing set	AUC 0.61 (0.53–0.69) Sens = 0.68; spec = 0.55; PPV = 0.72; NPV = 0.49	AUC 0.72 (0.65–0.79) Sens = 0.67; spec = 0.70; PPV = 0.80; NPV = 0.55	AUC 0.61 (0.51–0.71) Sens = 0.54; spec = 0.70; PPV = 0.72; NPV = 0.52	AUC = 0.72 (0.63–0.81) Sens = 0.57; spec = 0.82; PPV = 0.82; NPV = 0.57
5-HT drugs only	AUC 0.65 (0.55–0.76) Sens = 0.72; spec = 0.59; PPV = 0.72; NPV = 0.59	AUC 0.73 (0.63–0.83) Sens = 0.72; spec = 0.67; PPV = 0.76; NPV = 0.62	AUC 0.66 (0.52–0.80) Sens = 0.76; spec = 0.59; PPV = 0.74; NPV = 0.62	AUC 0.69(0.56–0.83) Sens = 0.70; spec = 0.67; PPV = 0.76; NPV = 0.60

The results of the other tested models are shown in Supplementary Table 9. AUC 95% confidence intervals are reported within parenthesis.
Sens sensitivity, spec specificity, PPV positive predictive value, NPV negative predictive value, 5-HT serotonergic drugs.
^aIncluding only subjects with a genetic score ≤30 percentile or ≥70 percentile see the section “Predictive modeling” of the main manuscript for more details.

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