In summary, our results provide mechanistic insight into how the PCa risk locus 17q12/HNF1B contributes to disease severity and progression through the germline-somatic interplay between HNF1B and TMPRSS2-ERG with a potential for transcriptionally mediating more genetic variance underpinning PCa susceptibility. The gene discussed is HNF1B; the disease is posterior cortical atrophy.