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Aim of this study was to examine the diagnostic uptake of targeted sequencing (TS), covering both coding and non\u2010coding regions, of a broad panel of 82 liver and lipid metabolism genes in patients with unexplained SLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 49 adult patients with SLD and a suspected genetic contribution. Genetic variants were detected through a customised TS panel, whereas the contribution of common genetic variation to the individual susceptibility to SLD was captured by a polygenic risk score (SLD\u2010PRS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A diagnosis of rare Mendelian disorder was established in 11 patients (22%), independently of age or family history. Rare variants possibly contributing to clinical phenotype were detected in additional 29 patients (59%). Increased SLD\u2010PRS values were detected in 17 patients (35%), enabling an increase in diagnostic uptake of 24%, especially in those without a strong family history (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). Genetic diagnosis allowed refinement of clinical management in 23 (47%) patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The diagnostic uptake of TS was 22% for Mendelian disorder and 59% for possible contribution to clinical phenotype in selected adult patients with SLD. Evaluation of common variants, as captured by SLD\u2010PRS, yields complementary information increasing the overall utility of the genetic examination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70010","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T07:06:57Z","timestamp":1739430417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic Uptake of Targeted Sequencing in Adults With Steatotic Liver Disease and a Suspected Genetic Contribution"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7820-6533","authenticated-orcid":false,"given":"Luisa","family":"Ronzoni","sequence":"first","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine Fondazione IRCCS ca' Granda Ospedale Maggiore Policlinico Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Pelusi","sequence":"additional","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine Fondazione IRCCS ca' Granda Ospedale Maggiore Policlinico Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1150-5568","authenticated-orcid":false,"given":"Vittoria","family":"Moretti","sequence":"additional","affiliation":[{"name":"Precisione Medicine Lab, Biological Resource Center and Department of Transfusion Medicine Fondazione IRCCS ca' Granda Ospedale Maggiore Policlinico Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Malvestiti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 Degli Studi di Milano  Milan 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