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

IF 2.7 3区医学 Q3 ONCOLOGY

Journal of Cancer Research and Clinical Oncology Pub Date : 2025-05-20 DOI:10.1007/s00432-025-06224-8

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

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引用次数: 0

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.

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整合转录组全关联研究和基于基因的关联分析确定霍奇金淋巴瘤的候选基因。

背景：全基因组关联研究（GWASs）已经确定了霍奇金淋巴瘤（HL）的许多易感位点，但其潜在的生物学机制尚不清楚。方法：利用来自UK Biobank和FinnGen的GWAS数据，结合基因型-组织表达（GTEx）和eQTL目录的表达数量性状位点（eQTL）统计数据，利用Omnibus转录组测试和表达参考汇总数据（OTTERS），以及eQTL基因组注释多标记分析（E-MAGMA）进行了大规模的基因水平关联研究。结论：这些发现突出了外源抗原呈递途径在HL中的作用，揭示了其潜在的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cancer Research and Clinical Oncology 医学-肿瘤学

CiteScore

4.00

自引率

2.80%

发文量

577

审稿时长

2 months

期刊介绍： The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.