INS and obesity due to melanocortin 4 receptor deficiency: After excluding obesity-related SNPs, MVMR analysis revealed direct causal effects of NAFLD (OR: 1.11, 95% CI: 1.05–1.17; P < 0.001), fasting insulin (OR per increase in natural log-transformed pmol/L fasting insulin: 3.11, 95% CI: 1.68–5.76; P < 0.001), and serum bioavailable testosterone levels (OR per increase in natural log-transformed nmol/L bioavailable testosterone: 1.90, 95% CI: 1.27–2.85; P = 0.002) on the risk of developing PCOS, respectively (Fig. 3, panel a; Additional file 1: Table S4).