Interplay between BTPD variant and PGS. (A) Each line represents the interplay between the effect of 1 of the top 10 BTPD variants and PGS on platelet count. The estimated effect size of the unique variant is represented by the purple segment of the bar and the PGS contribution is represented by the gray segment of the bar. The percentages given above the bars represent the frequencies of UKB participants carrying the BTPD variant and the predicted percentage of the population having a given PGS value for platelet count. The combination of the BTPD variant effect and PGS effect is together required to drop platelet count below the clinical threshold. The x-axis reports the effect size on platelet count in SD required to reduce the platelet count below the 150 × 10⁹/L threshold. (B) Receiver operating characteristic curve showing the prediction of VTE phenotypes using a predictive model based solely on rare BTPD variants for thrombosis (blue), a second model using only the PGS common variants (red), and a third one integrating rare BTPD- and common GWAS-variants (yellow). The area under the curve (AUC) indicates performance in variant classification. (C) Additive effect of the PGS for VTE derived from common GWAS-variants and 2 rare BTPD variants in PROC and 1 in PROS1. The x-axis shows the effects and directionalities of PGS effect estimates in SD (in green; ie, increased vs decreased risk) and the OR for the rare BTPD variant in OR (in orange). The contribution to VTE risk given by the 3 rare BTPD variants is constant, per variant, in carriers with VTE and “healthy” carriers without VTE (the orange portion of the bars). The distribution of PGS values differs significantly between the carriers with VTE and the “healthy” carriers (green portion of the bars).