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Background <p>Inflammatory bowel disease (IBD) is a common gastrointestinal disease related with the exposure of susceptible genes. Although genome-wide association studies (GWAS) have identified many loci associated with IBD, the more causative genes and their biological function seem still blank.</p> Methods <p>First, we use IBD GWAS from FINNGEN R11 dataset and the Genotype-Tissue expression project (GTE) V8 to conduct cross-tissue transcriptome association studies (TWAS). Second, Functional Summary-based Imputation (Fusion) and Multi-marker Analysis of Genomic Annotation (Magma) are performed to validate candidate genes. Third, conditionally independent genes are selected through conditional and joint analysis (COJO). Finally, we utilize mendelian randomization and colocalization to further screen candidate genes. Last, we show the function of genes through Gene. Multiple Association Network Integration Algorithm (MANIA) analysis.</p> Results <p>We identified two risk genes for IBD, including<i> TPRKB</i> in tibial artery, pancreas, stomach and testis tissues, and<i> RNF149</i> in basal ganglia of brain putamen. We found that<i> TPRKB</i> and<i> RNF149</i> have close relationship with<i> TP53RK</i> and<i> LAMP1</i> respectively.</p> Conclusion <p>Our study discovered two risk genes for IBD, which provided new insights to understand the pathogen of IBD at the genetic level.</p>

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RETRACTED ARTICLE: TPRKB and RNF149 identified as new inflammatory bowel disease susceptibility genes through multi-tissue transcriptome-wide association

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • Jianling Jia,
  • Zhenhua Dong,
  • Kai Yu,
  • Dingliang Zhao,
  • Daguang Wang

摘要

Background

Inflammatory bowel disease (IBD) is a common gastrointestinal disease related with the exposure of susceptible genes. Although genome-wide association studies (GWAS) have identified many loci associated with IBD, the more causative genes and their biological function seem still blank.

Methods

First, we use IBD GWAS from FINNGEN R11 dataset and the Genotype-Tissue expression project (GTE) V8 to conduct cross-tissue transcriptome association studies (TWAS). Second, Functional Summary-based Imputation (Fusion) and Multi-marker Analysis of Genomic Annotation (Magma) are performed to validate candidate genes. Third, conditionally independent genes are selected through conditional and joint analysis (COJO). Finally, we utilize mendelian randomization and colocalization to further screen candidate genes. Last, we show the function of genes through Gene. Multiple Association Network Integration Algorithm (MANIA) analysis.

Results

We identified two risk genes for IBD, including TPRKB in tibial artery, pancreas, stomach and testis tissues, and RNF149 in basal ganglia of brain putamen. We found that TPRKB and RNF149 have close relationship with TP53RK and LAMP1 respectively.

Conclusion

Our study discovered two risk genes for IBD, which provided new insights to understand the pathogen of IBD at the genetic level.