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Variants in the<jats:italic>PNPLA3<\/jats:italic>and<jats:italic>HSD17B13<\/jats:italic>genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We cross\u2010sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adjusting for age, sex, body mass index, and<jats:italic>PNPLA3<\/jats:italic>genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21\u20138.76,<jats:italic>p<\/jats:italic>\u2009=\u20090.019), an effect comparable to that of possessing the major<jats:italic>PNPLA3<\/jats:italic>risk variant. Notably, the effect of<jats:italic>PNPLA3<\/jats:italic>genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective<jats:italic>HSD17B13<\/jats:italic>variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13\u20131.16,<jats:italic>p<\/jats:italic>\u2009=\u20090.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91\u201333.86,<jats:italic>p<\/jats:italic>\u2009=\u20090.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors\u2014rather than genes or ethnicity\u2014may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajpa.24979","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T04:16:32Z","timestamp":1716437792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrating genetic and socioeconomic data to predict the progression of nonalcoholic fatty liver disease"],"prefix":"10.1002","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-6158","authenticated-orcid":false,"given":"Maria C.","family":"Rieman\u2010Klingler","sequence":"first","affiliation":[{"name":"Department of Anthropology University of California, San Diego La Jolla California USA"},{"name":"School of Medicine University of California, San Diego La Jolla California USA"},{"name":"Medical Scientist Training (MD\/PhD) Program 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