Schematic of two-stage study design using a parent cohort of patients on stable warfarin therapy. In the discovery cohort (left panel, we sequenced CALU in patients who had the largest or smallest residual dosing errors (shaded) within the parent cohort. In the second stage, significant (P < 0.05, FDR < 0.010) SNPs from the discovery stage were then genotyped in the remainder of the parent cohort (shaded, replication cohort 1, right panel). Predicted doses were based on a validated pharmacogenetics algorithm.9 CALU, calumenin; FDR, false-discovery rate; SNP; single-nucleotide polymorphism.