Kikuchi Masataka, Kobayashi Kaori, Nishida Nao, Sawai Hiromi, Sugiyama Masaya, Mizokami Masashi, Tokunaga Katsushi, Nakaya Akihiro
Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Medical Solutions Division, NEC Corporation, Tokyo, Japan.
Hum Genome Var. 2021 Jun 8;8(1):22. doi: 10.1038/s41439-021-00154-w.
Genome-wide association studies have been performed to identify common genetic variants associated with hepatitis B (HB). However, little is known about copy number variations (CNVs) in HB. In this study, we performed a genome-wide CNV analysis between 1830 healthy controls and 1031 patients with HB infection after quality control. Using signal calling by the Axiom Analysis Suite and CNV detection by PennCNV software, we obtained a total of 4494 CNVs across all individuals. The genes with CNVs that were found only in the HB patients were associated with the immune system, such as antigen processing. A gene-level CNV association test revealed statistically significant CNVs in the contactin 6 (CNTN6) gene. Moreover, we also performed gene-level CNV association tests in disease subgroups, including hepatocellular carcinoma patients, liver cirrhosis patients, and HBV carriers, including asymptomatic carriers and patients with HBV-derived chronic hepatitis. Our findings from germline cells suggested that patient-specific CNVs may be inherent genetic risk factors for HB.
全基因组关联研究已被用于识别与乙型肝炎(HB)相关的常见基因变异。然而,关于HB中的拷贝数变异(CNV)却知之甚少。在本研究中,我们在质量控制后对1830名健康对照和1031名HB感染患者进行了全基因组CNV分析。使用Axiom分析套件进行信号调用,并通过PennCNV软件进行CNV检测,我们在所有个体中总共获得了4494个CNV。仅在HB患者中发现的具有CNV的基因与免疫系统相关,如抗原加工。基因水平的CNV关联测试显示接触蛋白6(CNTN6)基因存在统计学上显著的CNV。此外,我们还在疾病亚组中进行了基因水平的CNV关联测试,包括肝细胞癌患者、肝硬化患者以及HBV携带者,包括无症状携带者和HBV衍生的慢性肝炎患者。我们在生殖细胞中的研究结果表明,患者特异性CNV可能是HB的内在遗传危险因素。