Extended Data Fig. 4: Variant quality control.

a–d, Calibration of quality score thresholds for variants that pass basic quality control (VQSR-pass, per-supercohort call-rate > 0.9, HWE equilibrium P-value in controls > 0.0001). Plots show the cumulative fraction of variants split by case-control P-value (two-tailed; Firth’s logistic regression). Thresholds were set at inflection points so that the majority of variants were retained while excluding a high proportion of variants strongly associated with case-control status. The following thresholds were applied: QD ≥ 6, MQRankSum ≥ −0.5, FS ≤ 14, and control-control minimum P-value ≥ 0.0001 (two-tailed; Firth’s logistic regression). e, Overview of variant QC steps. The first row shows the total number of called variants, the second row shows the number of variants passing basic QC, and the third row shows the number of variants passing strict QC. The strict QC variant filters were used in all analyses presented in this manuscript.