Computational protocol: Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

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Protocol publication

[…] The observed associations between SNPs and the protective effects on chronic hepatitis B or clearance of hepatitis virus B were assessed by chi-squared test with a two-by-two contingency table in allele frequency model. SNPs on chromosome X were removed because gender was not matched among HBV carriers, healthy controls and HBV-resolved individuals. A total of 597,789 SNPs and 590,278 SNPs passed the quality control filters in the GWAS stage; therefore, significance levels after Bonferroni correction for multiple testing were P = 8.36×10−8 (0.05/597,789) and P = 8.47×10−8 (0.05/590,278), respectively. For the replication study, 29 of 32 SNPs were successfully genotyped; therefore, we applied P = 0.0017 (0.05/29) as a significance level, and none of the 29 markers genotyped in the replication stage showed deviations from the Hardy-Weinberg equilibrium in healthy controls (P>0.01).The genetic inflation factor λ was estimated by applying the Cochrane-Armitage test on all SNPs and was found to be 1.056 and 1.030 in the GWAS using HBV carriers and healthy controls, and using HBV carriers and HBV-resolved individuals, respectively (). These results suggest that the population substructure should not have any substantial effect on statistical analysis. In addition, the principal component analysis in a total of 550 individuals in the GWAS stage together with the HapMap samples also revealed that the effect of population stratification was negligible ().Based on the genotype data of a total of 1,793 samples including 1,192 Japanese samples and 601 Korean samples in both GWAS and replication stages, haplotype blocks were estimated using the Gabriel’s algorithm using the Haploview software (v4.2) (). In the logistic regression analysis, two SNPs (rs9276431 and rs7768538) within the HLA-DQ locus were individually involved as a covariate (). Statistical analyses were performed using the SNP & Variation Suite 7 software (Golden Helix, MT, USA). […]

Pipeline specifications

Software tools Haploview, SVS
Application GWAS
Organisms Hepatitis B virus
Diseases Hepatitis B, Carcinoma, Hepatocellular, Liver Cirrhosis, Liver Diseases, Hepatitis B, Chronic