Gene-set enrichment study of the significantly associated SNPs.

<p>The functional enrichment among the flanking genes of identified susceptibility-associated SNPs (<i>P</i> < 5.0×10⁻⁴⁾ was estimated by gene ontology and pathway analyses implemented using DAVID and i-GSEA4GWAS softwares, respectively. The significance of the susceptibility-associated SNPs was estimated with a cutoff of <i>P</i> < 5.0×10⁻⁴. * <i>P</i>-values obtained from the pathway analysis are indicated.</p

Genotype-tissue expression analysis of rs7944135.

<p><b>A.</b> A <i>cis</i>-expression quantitative trait locus analysis and multi-tissue posterior probability for rs7944135 and <i>DTX4</i> are shown using the GTEx portal database. The five tissues with the highest statistical significance in the <i>cis</i>-expression quantitative trait locus analysis (<i>P</i>-value < 10⁻⁵) are indicated. This means that the expression level of <i>DTX4</i> significantly differs according to the allele of rs7944135 in those five tissues. <b>B.</b> The graphs for expression level of <i>DTX4</i> according to the genotypes of rs7944135 in five tissues. With the alteration to A, minor allele, of rs7944135, that was associated with acquisition of HBsAg seroclearance, the expression of <i>DTX4</i> is decreased.</p

ROI3 enriched with significant SNPs for HBsAg seroclearance in CHB patients.

<p>ROI3 enriched with significant SNPs for HBsAg seroclearance in CHB patients.</p

Haplotype analysis in the ROI for HBsAg seroclearance in patients with CHB.

<p>Haplotype analysis in the ROI for HBsAg seroclearance in patients with CHB.</p

Chromosomal distribution of the single-nucleotide polymorphisms (SNPs) associated with the seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB).

<p>The Manhattan plot shows the chromosomal distribution of the–log10 (<i>P</i> value) of SNPs. The threshold cutoff for the significant SNPs (<i>P</i> <10⁻⁵) is shown with horizontal line.</p

Clinical features of participants in the present study.

<p>Clinical features of participants in the present study.</p

Three regions of interest (ROIs) for susceptibility loci of HBsAg seroclearance.

<p>Three ROIs at 7p15.2, 5q14.1, and 11q12.1 are shown using LocusZoom (<i>top</i>). For the SNPs in the ROI, −log10 (<i>P</i> value) are plotted, and the significant SNPs are indicated. The section of the ROI is indicated with yellow bars. The recombination rates expressed in centimorgans (cM) per Mb (NCBI Build GRCh37) are also shown. The linkage disequilibrium values of the SNPs in the ROIs plotted using Haploview are shown (<i>bottom</i>). <i>D</i>′-based LD maps are shown for the two different data sets of our Korean cohort (KR) and the public data of the Beijing Han Chinese and Tokyo Japanese cohorts form 1000 Genomes Project data. The <i>D</i>′ scores for each paired SNP are indicated using different colors. As the LD increases, the color of the diamond becomes closer to red. The results show that both cohorts have significant LD among the SNPs within ROI. ROI1 and 2 was excluded for further analyses due to low LD (<i>r</i>^<i>2</i> < 0.5).</p