《Table 4 Allele discrepancy of rs506121,rs2071676,rs11040923 between cases and controls.》

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《New Gene Variants Associated with the Risk of Chronic HBV Infection》

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P values less than 0.05 in meta-analysis are indicated in bold DOCK8 Dedicator of cytokinesis 8；CA9 carbonic anhydrase 9；DNHD1 dynein heavy chain domain 1；ORodds ratio；CI confidence interval.*If the OR was calculated as C/T，then the frequency listed in th

In the first stage，we did not find any potentially functional gene variants that may have a relationship with HBVinfection at the Bonferroni genome-wide significance level（Fig.1）.Reasons accounting for this may be as follows:first，exome sequencing only focuses on genetic variation in the exome region，and is thus very likely to neglect those lying in the noncoding region（Wang et al.2018）；second，statistical power of classical single-variant based association tests for low-frequency and rare variants is low when the sample sizes are small（Lee et al.2014；Wang et al.2018）.In the following stage，we expanded our sample sizes and further conducted a TOF analysis to confirm the potential gene variants found in the discovery-phase.Twostage design is the standard strategy of genome-wide association study for discovering and validating the candidate genetic makers.Stage 2 is a replication study which focuses on the statistical significance discovered in stage 1.Previous study demonstrated that joint analysis of replication-based study result in increased power to detect genetic association（Skol et al.2006）.And for evaluating the significance of association between genetic factors and affected-unaffected phenotypes，Chi square test，Fisher’s exact test（Purcell et al.2007）and mixed regression model（Zhou and Stephens 2012）are the most popular methods designed for population matched and un-matched studyrespectively.In our study，we used Chi square test to perform the joint analysis on 30 variants in two populations.Combining the results of these two stages，we observed that cases in CHB group have significantly higher frequency of DOCK8-T allele and higher frequency of CA9—A allele than controls in clearance group（Table 4）.