Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population

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.