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Hepatic steatosis and fibrosis are highly heritable and genetic variation has also been associated with the risk of hepatocellular carcinoma (HCC) and hepatic decompensation. This review summarizes the state of the art of genetics and genomics in SLD, with particular emphasis on potential clinical utility. Variants in\/near genes including PNPLA3, TM6SF2, and HSD17B13 have been associated with cirrhosis and HCC in both MASLD and ALD, while others such as those in GCKR, TRIB1, and GPAM have been consistently associated with greater risk of hepatic steatosis in MASLD with much weaker effects if any on cirrhosis and HCC. While data on MetALD genetics are limited, we believe that the genetic risk factors for liver steatosis, cirrhosis, and HCC will be similar in MetALD compared to MASLD and ALD based on the largely shared genetic risk factors for MASLD and ALD. Finally, we discuss future directions in SLD genetics, notably genetically-defined disease subtypes, gene-environment interactions and their implications for therapy, and the utility of genetics in clinical risk stratification. Genetic studies have provided insight into important disease processes in SLD and may have an upcoming role in clinical care.<\/jats:p>","DOI":"10.3350\/cmh.2026.0477","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:03:38Z","timestamp":1782709418000},"page":"e2026.0477","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic and genomic insights across the steatotic liver disease spectrum"],"prefix":"10.3350","volume":"32","author":[{"given":"Jake P.","family":"Mann","sequence":"first","affiliation":[{"name":"Department of Immunology & Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK"},{"name":"Liver Unit, Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karn","family":"Wijarnpreecha","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, AZ, USA"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitchapong","family":"Prasitsumrit","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Tr\u00e9po","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, H\u00f4pital Universitaire de Bruxelles, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium"},{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth K.","family":"Speliotes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-6066","authenticated-orcid":true,"given":"Vincent L.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","first-page":"1027","volume-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 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