全转录组关联研究与基于基因的关联分析相结合，鉴定出霍奇金淋巴瘤的候选基因。
Integration of transcriptome-wide association study and gene-based association analysis identifies candidate genes for Hodgkin lymphoma.
作者信息
Jia Wen-Hui, Huang Chang-Ling, Zhang Wen-Li, He Yong-Qiao, Xue Wen-Qiong, Liao Ying, Zhao Zhi-Yang, Yang Meng-Xuan, Pei Lu, Jia Wei-Hua, Wang Tong-Min
机构信息
School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
出版信息
J Cancer Res Clin Oncol. 2025 May 20;151(5):171. doi: 10.1007/s00432-025-06224-8.
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.
背景
全基因组关联研究（GWAS）已确定了许多霍奇金淋巴瘤（HL）的易感基因座，但其潜在的生物学机制仍不清楚。
方法
利用英国生物银行和芬兰基因库的GWAS数据，以及基因型-组织表达（GTEx）和eQTL目录中的表达定量性状基因座（eQTL）统计数据，我们使用带有表达参考汇总数据的综合转录组测试（OTTERS）进行了大规模基因水平关联研究，并使用基因组注释的eQTL多标记分析（E-MAGMA）进行了基于基因的分析。
结果
我们确定了16个HL易感基因（FDR < 0.01），主要与免疫相关，包括HLA-DQA1、HLA-DQA2、HLA-DQB1、HLA-DRB1、HLA-DRB5、HLA-DMA和HLA-DPB1，以及参与细胞凋亡、RNA加工、转录调控和信号转导的基因。我们确定了5个新的可能基因，包括HLA-DMA、HLA-DPB1、LSM2、AAR2和NOTCH4。
结论
这些发现突出了外源性抗原呈递途径在HL中的作用，为潜在机制提供了线索。
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