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Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We analyzed data from 2203 adults (aged 40\u201369\u00a0years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (<jats:italic>n<\/jats:italic>\u2009=\u2009934) or a stable group (<jats:italic>n<\/jats:italic>\u2009=\u20091269). NAFLD was defined using a NAFLD-liver fat score\u2009&gt;\u2009-0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25\u20131.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-023-04291-4","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T11:38:22Z","timestamp":1688470702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study"],"prefix":"10.1186","volume":"21","author":[{"given":"Jun-Hyuk","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Oh","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9021-3856","authenticated-orcid":false,"given":"Yu-Jin","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"4291_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13098-020-00570-y","volume":"12","author":"AF Godoy-Matos","year":"2020","unstructured":"Godoy-Matos AF, Silva J\u00fanior WS, Valerio CM. 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