PNPLA3 and obesity due to melanocortin 4 receptor deficiency: In 414 209 individuals from UK Biobank, followed for a median time of 10.9 years, there was a synergistic interaction between PNPLA3 genotype, alcohol intake and obesity; subjects with all three 3 factors had an adjusted HCC risks 30 times higher than their counterparts without all 3 risk factors [65].