Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease

Background & AimsFatty liver disease (FLD) is a growing epidemic that expected to be the leading cause of end-stage within next decade. Both environmental and genetic factors contribute susceptibility FLD. Several variants contributing FLD have been identified in exome-wide association studies. However, there still missing hereditability indicating other are yet discovered.MethodsTo find genes involved FLD, we first examined missense nonsense with alanine aminotransferase at an level 425,671 participants from UK Biobank. We then validated fat content 8930 whom measurement was available, replicated 2 3 independent cohorts comprising 2621 individuals available biopsy.ResultsWe 190 independently associated after correcting for multiple testing Bonferroni method. The majority these were not previously this trait. Among those associated, striking enrichment influencing lipid metabolism. rs2792751 GPAM/GPAT1, gene encoding glycerol-3-phosphate acyltransferase, mitochondrial, rs429358 APOE, apolipoprotein E, as robustly adjusting testing. affect metabolism liver.ConclusionsWe novel GPAM APOE steatosis damage. These findings may help better elucidate onset progression. Fatty discovered. To biopsy. liver.