{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:54:28Z","timestamp":1791345268772,"version":"4.3.1"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Individuals with genetic polymorphisms in <jats:italic>UGT1A1<\/jats:italic> exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A genome\u2010wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but <jats:italic>not<\/jats:italic> associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an \u2018elevated\u2019 LBT\u2014and how this differs by PGS\u2014was assessed through competing risk survival analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study included 157\u2009005 and 166\u2009871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10\u2010year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma\u2010glutamyltransferase (GGT) and the 10\u2010year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10\u2010year risk was .38%. Accordingly, the 10\u2010year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). Similar results were apparent for Fibrosis\u20104 index, total bilirubin, and platelet count.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16114","type":"journal-article","created":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T08:09:27Z","timestamp":1729325367000},"page":"3260-3273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interpreting elevated liver blood test results through a genetic lens: A genome\u2010wide association study"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-1083","authenticated-orcid":false,"given":"Hamish","family":"Innes","sequence":"first","affiliation":[{"name":"School of Health and Life Sciences Glasgow Caledonian University  Glasgow UK"},{"name":"BBV\/STI team, Public Health Scotland  Glasgow UK"},{"name":"Lifespan and Population Health University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Buch","sequence":"additional","affiliation":[{"name":"Medical Department 1 University Hospital Dresden  Dresden TU Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kendall","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair University of Edinburgh  Edinburgh UK"},{"name":"Edinburgh Pathology University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-1471","authenticated-orcid":false,"given":"Jonathan A.","family":"Fallowfield","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra Neil","family":"Guha","sequence":"additional","affiliation":[{"name":"NIHR Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and the University of Nottingham  Nottingham UK"},{"name":"Nottingham Digestive Diseases Centre, School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5684"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02277-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314924"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.1999.01984.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-058967"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta13250"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta17280"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-007516"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ueg2.12109"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_10_12_1","unstructured":"FryD AlmondR MoffatS GordonM SinghP.UK biobank project. 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