PNPLA3 and type 2 diabetes mellitus: Although pleiotropic effects have been reported for both PNPLA3 and GCKR – which may violate this ‘Mendelian randomization’ assumption40; it should be noted that these variants have opposing pleiotropic effects on plasma lipids,24, 29 and risk of type 2 diabetes and coronary artery disease,30, 31, 32 as summarized in Table S3.