Increased platelet reactivity via PAR-1 at rs10886430 is due to decreased expression of GRK5. Box plots showing the relationships between the genotype of rs10886430 and the reactivity of platelets to PAR-1 (after adjustment for covariates) in 546 participants in the Cambridge PFC (A) and platelet expression of GRK5 measured using probe ID:3190239 of the Illumina HumanHT-12 v4.0 Expression BeadChip microarray in 388 donors (B), after adjustment for technical variation. The thick horizontal bars indicate the median of each conditional distribution and the lower and upper hinges indicate the 25th and 75th percentiles, respectively, of each distribution. The whiskers extend no further than 1.5 interquartile ranges from the hinges. (C) The genetic association between PAR-1 reactivity and rs10886430 in intron 1 of GRK5 colocalizes with the binding of the transcription factors GATA-1 and MEIS1 in human MKs and an enhancer specific to the human MK blood cell lineage. Top to bottom: the strength of evidence for the association between genetic variants in the GRK5 locus and PAR-1 reactivity, measured by −log₁₀(P value); the binding sites of the transcription factors GATA-1, RUNX1, FLI1, and MEIS1 in human MKs; ATAC-seq read depth indicating regions of open chromatin in human MKs; ChIP-seq read depth measuring the histone modifications H3K4me1, HSK4me3, and H3K27ac in human MKs; human MK enhancer sites inferred from the ATAC-seq and ChIP-seq data; and a model of the GRK5 gene with exons indicated by rectangles.