{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:33:19Z","timestamp":1790249599098,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Steatotic liver disease (SLD) is the most common liver disease worldwide, affecting 30% of the global population. It is strongly associated with the interplay of genetic and lifestyle\u2010related risk factors. The genetic variant accounting for the largest fraction of SLD heritability is\n PNPLA3<\/jats:italic>\n I148M, which is carried by 23% of the western population and increases the risk of SLD two to three\u2010fold. However, identification of variant carriers is not part of routine clinical care and prevents patients from receiving personalised care.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analysed MRI images and common genetic variants in\n PNPLA3, TM6SF2, MTARC1, HSD17B13<\/jats:italic>\n and\n GCKR<\/jats:italic>\n from a cohort of 45\u2009603 individuals from the UK Biobank. Proton density fat fraction (PDFF) maps were generated using a water\u2010fat separation toolbox, applied to the magnitude and phase MRI data. The liver region was segmented using a U\u2010Net model trained on 600 manually segmented ground truth images. The resulting liver masks and PDFF maps were subsequently used to calculate liver PDFF values. Individuals with (PDFF \u2265\u20095%) and without SLD (PDFF <\u20095%) were selected as the study cohort and used to train and test a Vision Transformer classification model with five\u2010fold cross validation. We aimed to differentiate individuals who are homozygous for the\n PNPLA3<\/jats:italic>\n I148M variant from non\u2010carriers, as evaluated by the area under the receiver operating characteristic curve (AUROC). To ensure a clear genetic contrast, all heterozygous individuals were excluded. To interpret our model, we generated attention maps that highlight the regions that are most predictive of the outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Homozygosity for the\n PNPLA3<\/jats:italic>\n I148M variant demonstrated the best predictive performance among five variants with AUROC of 0.68 (95% CI: 0.64\u20130.73) in SLD patients and 0.57 (95% CI: 0.52\u20130.61) in non\u2010SLD patients. The AUROCs for the other SNPs ranged from 0.54 to 0.57 in SLD patients and from 0.52 to 0.54 in non\u2010SLD patients. The predictive performance was generally higher in SLD patients compared to non\u2010SLD patients. Attention maps for\n PNPLA3<\/jats:italic>\n I148M carriers showed that fat deposition in regions adjacent to the hepatic vessels, near the liver hilum, plays an important role in predicting the presence of the I148M variant.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our study marks novel progress in the non\u2010invasive detection of homozygosity for\n PNPLA3<\/jats:italic>\n I148M through the application of deep learning models on MRI images. Our findings suggest that\n PNPLA3<\/jats:italic>\n I148M might affect the liver fat distribution and could be used to predict the presence of\n PNPLA3<\/jats:italic>\n variants in patients with fatty liver. The findings of this research have the potential to be integrated into standard clinical practice, particularly when combined with clinical and biochemical data from other modalities to increase accuracy, enabling easier identification of at\u2010risk individuals and facilitating the development of tailored interventions for\n PNPLA3<\/jats:italic>\n I148M\u2010associated liver disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70164","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T10:31:00Z","timestamp":1749205860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deep Learning Reveals Liver MRI Features Associated With\n PNPLA3<\/i>\n I148M in Steatotic Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9893-645X","authenticated-orcid":false,"given":"Yazhou","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P. M.","family":"Laevens","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Lemainque","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav Anton","family":"M\u00fcller\u2010Franzes","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9115-3228","authenticated-orcid":false,"given":"Tobias","family":"Seibel","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Dlugosch","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Clusmann","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus TUD Dresden University of Technology Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul\u2010Henry","family":"Koop","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus TUD Dresden University of Technology Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongpeng","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niharika","family":"Jakhar","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Visceral and Transplantation Surgery University Hospital RWTH Aachen Aachen 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University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9926-6070","authenticated-orcid":false,"given":"Joel","family":"Joy","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Loomba","sequence":"additional","affiliation":[{"name":"MASLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine University of California San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-0345","authenticated-orcid":false,"given":"Luca","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation University of Milan Milan Italy"},{"name":"Precision Medicine and Biological Resource Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob Nikolas","family":"Kather","sequence":"additional","affiliation":[{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus TUD Dresden University of Technology Dresden Germany"},{"name":"Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus TUD Dresden University of Technology Dresden Germany"},{"name":"Medical Oncology, National Center for Tumor Diseases (NCT) University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titus J.","family":"Brinker","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Herzog","sequence":"additional","affiliation":[{"name":"Else 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University of Technology Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Truhn","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-9246","authenticated-orcid":false,"given":"Carolin V.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen Aachen Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus TUD Dresden University of Technology Dresden 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