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Background <p>Nonalcoholic fatty liver disease (NAFLD) is an escalating health concern, with genetic factors playing a substantial role. This study aimed to establish and validate a polygenic risk score for East Asian populations (PRS-EA).</p> Methods <p>A meta-analysis of genome-wide association studies on NAFLD in East Asian populations was conducted to develop a PRS-EA model. This model was subsequently validated in the Kailuan cohort by exploring its association with NAFLD development and progression.</p> Results <p>A PRS-EA model involving four SNPs (rs2896019, rs3810622, rs58542926, and rs1260326) was constructed. Individuals with PRS-EA scores exceeding 2.33 were associated with a 53% (95% confidence interval, 3%-126%) increased risk of NAFLD development and 50% (95% confidence interval: 3%-120%) of NAFLD progression. A positive joint association was observed between higher PRS and lipid dysfunction in relation to NAFLD occurrence. Hypertension was found to amplify the association between higher PRS and NAFLD progression (hazard ratio: 3.07 vs. 1.22, <i>P </i>for interaction=0.015).</p> Conclusion <p>This study developed a PRS model specific to East Asian populations, highlighting the potential utility of PRS-EA in assessing and managing NAFLD risk, particularly in individuals with lipid metabolic dysfunction and hypertension</p> Graphical abstract <p></p>

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Association of non-alcoholic fatty liver polygenic risk scores with the incident and progressive non-alcoholic fatty liver disease in Chinese population

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • Yang Zhou,
  • Di Zhou,
  • Shuohua Chen,
  • Chenlu Yang,
  • Shutong Wu,
  • Xiaomo Wang,
  • Yanqi Lan,
  • Ying Lu,
  • Mengge Zhou,
  • Shouling Wu,
  • Man Li,
  • Li Wang

摘要

Background

Nonalcoholic fatty liver disease (NAFLD) is an escalating health concern, with genetic factors playing a substantial role. This study aimed to establish and validate a polygenic risk score for East Asian populations (PRS-EA).

Methods

A meta-analysis of genome-wide association studies on NAFLD in East Asian populations was conducted to develop a PRS-EA model. This model was subsequently validated in the Kailuan cohort by exploring its association with NAFLD development and progression.

Results

A PRS-EA model involving four SNPs (rs2896019, rs3810622, rs58542926, and rs1260326) was constructed. Individuals with PRS-EA scores exceeding 2.33 were associated with a 53% (95% confidence interval, 3%-126%) increased risk of NAFLD development and 50% (95% confidence interval: 3%-120%) of NAFLD progression. A positive joint association was observed between higher PRS and lipid dysfunction in relation to NAFLD occurrence. Hypertension was found to amplify the association between higher PRS and NAFLD progression (hazard ratio: 3.07 vs. 1.22, P for interaction=0.015).

Conclusion

This study developed a PRS model specific to East Asian populations, highlighting the potential utility of PRS-EA in assessing and managing NAFLD risk, particularly in individuals with lipid metabolic dysfunction and hypertension

Graphical abstract