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Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma\u2010glutamyl transferase (<jats:styled-content style=\"fixed-case\">GGT<\/jats:styled-content>). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from participants in twin and twin\u2010family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (<jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content>) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum <jats:styled-content style=\"fixed-case\">GGT<\/jats:styled-content>, alanine aminotransferase (<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>), or aspartate aminotransferase (<jats:styled-content style=\"fixed-case\">AST<\/jats:styled-content>) as outcomes. We conducted genome\u2010wide association analyses for <jats:styled-content style=\"fixed-case\">GGT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ALT<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">AST<\/jats:styled-content> separately in the group reporting excessive alcohol intake (<jats:italic>N<\/jats:italic>\u00a0=\u00a0951) and a low\u2010intake group reporting 14 drinks or fewer per week (<jats:italic>N<\/jats:italic>\u00a0=\u00a08,716), and compared results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Abnormal <jats:styled-content style=\"fixed-case\">GGT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> among excessive drinkers were associated with higher <jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content>, triglycerides, insulin, uric acid, C\u2010reactive protein, ferritin, and transferrin saturation; and with lower high\u2010density\u2010lipoprotein cholesterol. Abnormal <jats:styled-content style=\"fixed-case\">AST<\/jats:styled-content> was associated with triglycerides, ferritin, and transferrin saturation. <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> was significantly associated with variants at reported genetic loci for alcoholic liver disease (<jats:italic><jats:styled-content style=\"fixed-case\">PNPLA<\/jats:styled-content>3<\/jats:italic>, rs738409, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0076; <jats:italic><jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>6<jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>2<\/jats:italic>, rs10401969, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0076; <jats:italic><jats:styled-content style=\"fixed-case\">HSD<\/jats:styled-content>17B13<\/jats:italic>, rs10433879, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0024).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13949","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T16:52:02Z","timestamp":1545929522000},"page":"473-482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biomarker and Genomic Risk Factors for Liver Function Test Abnormality in Hazardous Drinkers"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-0876","authenticated-orcid":false,"given":"John B.","family":"Whitfield","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute  Brisbane Queensland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu","family":"Zhu","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute  Brisbane Queensland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A. 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