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Liver, Pancreas and Biliary Tract| Volume 53, ISSUE 11, P1435-1442, November 2021

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Genetic predisposition, lifestyle risk, and obesity associate with the progression of nonalcoholic fatty liver disease

  • Author Footnotes
    1 These authors are contributed equally to this work.
    Zhenqiu Liu
    Footnotes
    1 These authors are contributed equally to this work.
    Affiliations
    State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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  • Author Footnotes
    1 These authors are contributed equally to this work.
    Chen Suo
    Footnotes
    1 These authors are contributed equally to this work.
    Affiliations
    Fudan University Taizhou Institute of Health Sciences, Taizhou, China

    Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China

    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
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  • Renjia Zhao
    Affiliations
    Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China

    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
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  • Huangbo Yuan
    Affiliations
    State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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  • Li Jin
    Affiliations
    State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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  • Tiejun Zhang
    Affiliations
    Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China

    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
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  • Xingdong Chen
    Correspondence
    Corresponding author at: State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.
    Affiliations
    State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
    Search for articles by this author
  • Author Footnotes
    1 These authors are contributed equally to this work.
Published:August 02, 2021DOI:https://doi.org/10.1016/j.dld.2021.07.009

      Abstract

      Background

      Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide. We aim to identify the factors promoting NAFLD progression.

      Methods

      UK Biobank study participants were diagnosed for whether NAFLD presented at baseline. Cox regression model was used to examine the association of risk factors with incident diseases (significant liver diseases [SLDs], type 2 diabetes [T2D], cardiovascular diseases [CVDs], chronic kidney diseases [CKDs], and cancers) among NAFLD cases.

      Results

      Of 78 283 individuals, 35 159 (44.9%) were females, and the mean (SD) age was 57.56 (7.90) years. Compared with participants had both low genetic and lifestyle risk, individuals with both high genetic and lifestyle risk had a hazard ratio of 1.64 (95% CI 1.32–2.03) for SLDs, 1.16 (1.08–1.24) for T2D, 1.25 (1.13–1.37) for CVDs, 1.33 (1.18–1.49) for CKDs, and 1.13 (1.05-1.22) for cancers. Compared with participants who were non-obese and had low genetic risk, those with obesity and high genetic risk had an 75% (95% CI 38–123%), 147% (128–167%), 46% (33–61%), and 76% (56–99%) increased risk for developing SLDs, T2D, CVDs, and CKDs, respectively. The population-attributable fractions suggested that lifestyle risk and obesity contributed more to the progression of NAFLD than genetic risk.

      Conclusion

      Adhering to a healthy lifestyle and avoiding obesity are important to prevent NAFLD progression.

      Keywords

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      Linked Article

      • Genes and lifestyle: Which of the two is more relevant in driving NAFLD progression?
        Digestive and Liver DiseaseVol. 53Issue 11
        • Preview
          A wide spectrum of factors conjointly operate in the pathogenesis of NAFLD and in liver disease progression towards advanced liver disease and comorbidities [1]. At one extreme we find genetic factors: they provide mechanism(s) facilitating liver fat accumulation well before birth, as expressed by epigenetic studies [2], and are operative throughout life. In recent years several studies have shown that a lot of gene polymorphisms are associated with an increased risk of NAFLD, variably linked with obesity, with the risk of cardiovascular events, with the risk of progression to hepatocellular cancer [3].
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