Integration of transcriptome-wide association study and gene-based association analysis identifies candidate genes for Hodgkin lymphoma

Abstract Background Genome-wide association studies (GWASs) have pinpointed many susceptibility loci for Hodgkin Lymphoma (HL), but their underlying biological mechanisms remain unclear. Methods Utilizing GWAS data from the UK Biobank and FinnGen, along with expression quantitative trait loci (eQTL)...

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Main Authors: Wen-Hui Jia, Chang-Ling Huang, Wen-Li Zhang, Yong-Qiao He, Wen-Qiong Xue, Ying Liao, Zhi-Yang Zhao, Meng-Xuan Yang, Lu Pei, Wei-Hua Jia, Tong-Min Wang
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Journal of Cancer Research and Clinical Oncology
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Online Access:https://doi.org/10.1007/s00432-025-06224-8
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Summary:Abstract Background Genome-wide association studies (GWASs) have pinpointed many susceptibility loci for Hodgkin Lymphoma (HL), but their underlying biological mechanisms remain unclear. Methods Utilizing GWAS data from the UK Biobank and FinnGen, along with expression quantitative trait loci (eQTL) statistics from the Genotype-Tissue Expression (GTEx) and the eQTL Catalogue, we carried out a large-scale gene-level association study using Omnibus Transcriptome Test with Expression Reference Summary data (OTTERS), and gene-based analysis with eQTL Multi-marker Analysis of Genomic Annotation (E-MAGMA). Results We identified sixteen susceptibility genes for HL (FDR < 0.01), primarily immune-related, including HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB5, HLA-DMA, and HLA-DPB1, alongside genes involved in apoptosis, RNA processing, transcriptional regulation, and signal transduction. We identified five novel plausible genes, including HLA-DMA, HLA-DPB1, LSM2, AAR2, and NOTCH4. Conclusion These findings highlight the role of the exogenous antigen presentation pathway in HL, shedding light on potential mechanisms.
ISSN:1432-1335