As shown in Figure 3, the strong association with PSA measurement (P=7.16 × 10–43) validated our genetic instruments, while the enrichment of metabolic traits such as BMI-adjusted waist–hip ratio (WHR) (P=1.32 × 10–26), high-density lipoprotein (HDL) cholesterol measurement (P=2.38 × 10–22), and body mass index (P=1.71 × 10–20) aligned with epidemiological evidence linking obesity to aggressive PCa. This evidence concerns the gene KLK3 and obesity due to melanocortin 4 receptor deficiency.