<p>Characterization of dQTLs. <b>A,</b> Summary of all 35 dQTLs involving 25 unique SNPs. Dot size and color indicate the magnitude and direction of association (as OR), and background shading indicates dQTL discovered strategy. <b>B,</b> Forest plot of OR and 95% confidence interval for dQTL associations across 1,991 prostate tumors. Background shading indicates <i>Q</i> < 0.1. The middle covariate indicates the driver mutation, and the right heatmap indicates cohorts included in the analysis. <b>C,</b> Summary of molecular and clinical characterization of dQTLs. Gray indicates dQTL was association with methylation (meQTL), RNA abundance (eQTL), protein abundance (pQTL), transcription factor–binding, histone modification, ISUP GG, BCR, or risk of prostate cancer diagnosis (PCa Risk). Left covariate indicates somatic drivers. <b>D,</b> rs11203152 is located within regulatory dense region. Tracks show chromatin looping anchored by RNAPII, RAD21, AR, or ERG in RWPE-1, LNCaP, VCaP, or DU145 cell lines. <b>E,</b> The number of chromatin loops was higher than expected by chance in LNCaP and VCaP cell lines. Barplots shows the number of anchors within one Mbp of rs11203152. Bottom covariate indicates cell line and target, whereas background shading indicates significant enrichment (<i>Q</i> < 0.05). The red X indicates the expected number of chromatin loop anchors based on 100,000 randomly sampled, equally sized regions. <b>F,</b> dQTLs may explain differences in somatic mutation frequencies across ancestries. Barplot shows the risk of acquiring a <i>FOXA1</i> SNV or T2E in African (green) or Asian (purple) ancestry relative to European ancestry. The estimated percent of this risk explained by rs848048 (<i>FOXA1</i>) or rs11203152 (T2E) is indicated above the bar. The top covariate indicates ancestry: African in green and Asian in purple. Somatic mutation direction relative to European ancestry is indicated as higher (pink) <i>vs.</i> lower (teal). <b>G,</b> Schematic overview of primary prostate cancer evolution into ISUP GGs. The vertical blue arrow illustrates the temporal relationship between the germline context and driver mutations and the roles they play in tumor evolution. The germline SNPs (bottom) were found to be associated with driver acquisition illustrated by connecting lines. The somatic driver mutation frequency across IMSs is visualized using barplots. The horizontal arrow indicates increasing genomic instability across subtypes and ISUP GGs (<a href="#bib9" target="_blank">9</a>). The Sankey plot connects the IMSs and ISUP GGs, indicating the nondeterministic association between driver acquisition and clinical presentation, while noting the potential role of the tumor microenvironment (<a href="#bib90" target="_blank">90</a>) and epigenetics (<a href="#bib45" target="_blank">45</a>) (<b>G,</b> Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.)</p>