Enhancing disease risk gene discovery by integrating transcription factor-linked trans-variants into transcriptome-wide association analyses Journal Article
| Authors: | He, J.; Perera, D.; Wen, W.; Ping, J.; Li, Q.; Lyu, L.; Chen, Z.; Shu, X.; Long, J.; Cai, Q.; Shu, X. O.; Yin, Z.; Zheng, W.; Long, Q.; Guo, X. |
| Article Title: | Enhancing disease risk gene discovery by integrating transcription factor-linked trans-variants into transcriptome-wide association analyses |
| Abstract: | Transcriptome-wide association studies (TWAS) have been successful in identifying disease susceptibility genes by integrating cis-variants predicted gene expression with genome-wide association studies (GWAS) data. However, trans-variants for predicting gene expression remain largely unexplored. Here, we introduce transTF-TWAS, which incorporates transcription factor (TF)-linked trans-variants to enhance model building for TF downstream target genes. Using data from the Genotype-Tissue Expression project, we predict gene expression and alternative splicing and applied these prediction models to large GWAS datasets for breast, prostate, lung cancers and other diseases. We demonstrate that transTF-TWAS outperforms other existing TWAS approaches in both constructing gene expression prediction models and identifying disease-associated genes, as shown by simulations and real data analysis. Our transTF-TWAS approach significantly contributes to the discovery of disease risk genes. Findings from this study shed new light on several genetically driven key TF regulators and their associated TF–gene regulatory networks underlying disease susceptibility. © The Author(s) 2024. |
| Keywords: | controlled study; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; metabolism; genetic predisposition to disease; breast cancer; gene expression; gene expression profiling; genome-wide association study; lung cancer; transcription factor; breast neoplasms; transcription factors; prostatic neoplasms; breast tumor; prostate tumor; alternative splicing; alternative rna splicing; gene regulatory network; disease predisposition; genetic predisposition; transcriptome; schizophrenia; rna sequence; gene regulatory networks; procedures; autism; humans; gene discovery; human; male; article |
| Journal Title: | Nucleic Acids Research |
| Volume: | 53 |
| Issue: | 1 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-01-13 |
| Start Page: | gkae1035 |
| Language: | English |
| DOI: | 10.1093/nar/gkae1035 |
| PUBMED: | 39535029 |
| PROVIDER: | scopus |
| PMCID: | PMC11724290 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
