Prevalence of hepatitis B genotype and viral basic core promoter and precore mutations among teenagers in Macao: relationship with hepatocellular carcinoma development

Chronic hepatitis B virus (HBV) infection is a global problem and over 75% of cases are reported in the Asia Pacific region. Infection can lead to progressive liver disease, cirrhosis and hepatocellular carcinoma (HCC). Previous studies suggest the prevalence of HBV carriers in Macau to be approximately 10% of the population. This study aims to investigate the prevalence of HBV genotypes among HBV-positive teenagers in Macao and the prevalence of base core promoter (BCP) and precore (PreC) mutations in the viral genome. In addition, through monitoring aminotransferase and alpha-fetoprotein, it aims to investigate relationships among HBV genotypes, BCP/PreC mutations and HCC development. This study recruited 1991 teenagers in Macau in 2008, and the PreS1/S2, BCP and PreC region of the HBV genome from 34 HBsAg-positive subjects were amplified and sequenced to determine HBV genotype and presence of HCC-associated mutations. Results suggested that the average rate of HBV infection among secondary school teenagers in Macao is low, and HBV genotype B and C viruses were found to predominate in Macao. The BCP/PreC mutations A1762T, G1764A, G1896A and C1766T were identified in 2.9-11.7% of subjects. However, no significant relationship was observed between HBV genotype, BCP/PreC mutations and HCC development

Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. Wemeta-analyzedGWAS data from18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.Clinical epidemiolog