GWAS meta-analyses of T2DM have implicated p.I148M in PNPLA3 and p.E167K in TM6SF2 as significant risk loci (albeit with very modest effect sizes compared with their effects on liver disease)55 and Mendelian randomisation studies indicate a causal role in determining insulin resistance mediated by the degree of liver damage.48 The gene discussed is PNPLA3; the disease is liver disorder.