PNPLA3 and obesity due to melanocortin 4 receptor deficiency: We found that high alcohol intake (>14 units per week), obesity (BMI > 30 kg m−2) and T2D also amplified the effect of PNPLA3 p.Ile148Met on hepatocellular carcinoma (HCC) and all-cause liver disease (Fig. 4 and Supplementary Table 15).