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Background <p>This study aimed to explore the causal association between imaging measurement indicators of major internal organs and liver lesions using a two-sample Mendelian randomization (MR) method.</p> Methods <p>Data from the UK Biobank and GWAS Catalog platform were used to select single nucleotide polymorphisms (SNPs) associated with MRI or derived measurement results of various organ indicators as genetic instrumental variables. Data from the FinnGen project’s R9 version were used to select liver lesion outcomes, such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic cirrhosis, and primary hepatocellular carcinoma (HCC). UVMR analysis were utilized variable-by-variable, and MVMR was used to adjust for confounding on significant variables. Steiger directional test, heterogeneity, pleiotropy, and sensitivity tests were conducted to enhance reliability.</p> Results <p>Univariate Mendelian randomization analysis (UVMR) indicated that liver volume (LV), liver fat (LF), and subcutaneous adipose tissue measurement (SATM) are risk factors for NAFLD. The multivariable MR (MVMR) results for NAFLD showed that LV and LF remained significant, while SATM did not. For cirrhosis (NAC), UVMR suggested that LV, LF, and SATM are risk factors, but MVMR results showed that only LV and LF remained significant. Additionally, pancreatic volume (PV) was found to be a protective factor, while splenic volume (SV) was a pathogenic factor for NAC. For HCC, both UVMR and MVMR analyses suggested that LF and liver iron (LI) are risk factors, while SATM did not remain significant in the MVMR analysis.</p> Conclusions <p>LV, LF, and SATM are associated with NAFLD. In the NAC stage, additional pathogenic effects of PV and SV were observed. The related results for LF and LI support the pathogenic effect of liver iron factors in the HCC stage.</p>

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Causal relationship analysis of MRI measurements of major human internal organs and liver disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月11日

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  • Huanyu Wu,
  • Danjing Zhou,
  • Jinggang Zhu,
  • Jianchun Tu

摘要

Background

This study aimed to explore the causal association between imaging measurement indicators of major internal organs and liver lesions using a two-sample Mendelian randomization (MR) method.

Methods

Data from the UK Biobank and GWAS Catalog platform were used to select single nucleotide polymorphisms (SNPs) associated with MRI or derived measurement results of various organ indicators as genetic instrumental variables. Data from the FinnGen project’s R9 version were used to select liver lesion outcomes, such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic cirrhosis, and primary hepatocellular carcinoma (HCC). UVMR analysis were utilized variable-by-variable, and MVMR was used to adjust for confounding on significant variables. Steiger directional test, heterogeneity, pleiotropy, and sensitivity tests were conducted to enhance reliability.

Results

Univariate Mendelian randomization analysis (UVMR) indicated that liver volume (LV), liver fat (LF), and subcutaneous adipose tissue measurement (SATM) are risk factors for NAFLD. The multivariable MR (MVMR) results for NAFLD showed that LV and LF remained significant, while SATM did not. For cirrhosis (NAC), UVMR suggested that LV, LF, and SATM are risk factors, but MVMR results showed that only LV and LF remained significant. Additionally, pancreatic volume (PV) was found to be a protective factor, while splenic volume (SV) was a pathogenic factor for NAC. For HCC, both UVMR and MVMR analyses suggested that LF and liver iron (LI) are risk factors, while SATM did not remain significant in the MVMR analysis.

Conclusions

LV, LF, and SATM are associated with NAFLD. In the NAC stage, additional pathogenic effects of PV and SV were observed. The related results for LF and LI support the pathogenic effect of liver iron factors in the HCC stage.