Scholarlink

Background <p>Hepatic steatosis is a highly prevalent metabolic condition and a major contributor to chronic liver disease, particularly in Asian populations. This study was conducted to identify genetic variants associated with the severity of ultrasound-defined hepatic steatosis in a Taiwanese Han population and evaluate the variants’ biological relevance through cross-ancestry meta-analysis and functional validation.</p> Methods <p>We conducted a genome-wide association study (GWAS) of 133,895 individuals with data in the Genetic Biobank of China Medical University Hospital. Hepatic steatosis severity was graded on an ordinal scale (0–3) using standardised ultrasonographic criteria. The polygenic risk score (PRS) under continuous shrinkage (CS) approach was used to construct a PRS for genetic risk stratification across severity grades.</p> <p>Findings:</p> <p>In the GWAS, we identified 1,229 single-nucleotide polymorphisms associated with hepatic steatosis severity (<i>P</i> &lt; 1 × 10⁻<sup>5</sup>), with the strongest signals discovered at the <i>PNPLA3</i> locus (rs738408 and rs738409). The PRS-CS model exhibited strong discriminative performance (area under the receiver operating characteristic curve = 0.875) and a clear dose–response relationship with ultrasound-defined steatosis severity, substantially outperforming the risk model based on body mass index only. In vitro assays confirmed significantly increased lipid accumulation and intracellular triglyceride content in I148M-expressing hepatocytes under lipid-loading conditions.</p> <p>Interpretation:</p> <p>This study delineates the genetic landscape of ultrasound-defined hepatic steatosis severity in a large Taiwanese Han population and demonstrates the robust ability of the PRS to predict disease stage.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genome-wide association and polygenic risk score analyses of MASLD-related hepatic steatosis severity in a Taiwanese Han population

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

查看全文
  • Ting-Yuan Liu,
  • Jai-Sing Yang,
  • Yu-Chia Chen,
  • Shih-Chang Tsai,
  • Yu-Jen Chiu,
  • Chi-Chou Liao,
  • Yen‐Ting Chang,
  • Woei-Cheang Shyu,
  • Long-Bin Jeng,
  • Fuu-Jen Tsai

摘要

Background

Hepatic steatosis is a highly prevalent metabolic condition and a major contributor to chronic liver disease, particularly in Asian populations. This study was conducted to identify genetic variants associated with the severity of ultrasound-defined hepatic steatosis in a Taiwanese Han population and evaluate the variants’ biological relevance through cross-ancestry meta-analysis and functional validation.

Methods

We conducted a genome-wide association study (GWAS) of 133,895 individuals with data in the Genetic Biobank of China Medical University Hospital. Hepatic steatosis severity was graded on an ordinal scale (0–3) using standardised ultrasonographic criteria. The polygenic risk score (PRS) under continuous shrinkage (CS) approach was used to construct a PRS for genetic risk stratification across severity grades.

Findings:

In the GWAS, we identified 1,229 single-nucleotide polymorphisms associated with hepatic steatosis severity (P < 1 × 10⁻5), with the strongest signals discovered at the PNPLA3 locus (rs738408 and rs738409). The PRS-CS model exhibited strong discriminative performance (area under the receiver operating characteristic curve = 0.875) and a clear dose–response relationship with ultrasound-defined steatosis severity, substantially outperforming the risk model based on body mass index only. In vitro assays confirmed significantly increased lipid accumulation and intracellular triglyceride content in I148M-expressing hepatocytes under lipid-loading conditions.

Interpretation:

This study delineates the genetic landscape of ultrasound-defined hepatic steatosis severity in a large Taiwanese Han population and demonstrates the robust ability of the PRS to predict disease stage.