Abstract LB-176: Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese

Abstract

Abstract The etiology of persistent hepatitis B virus (HBV) infection is complex and multifactorial, polygenic event with viral, environmental and genetic components being considered as the risk factors. Genome-wide association study (GWAS) has been applied into the exploration of genetic etiology of persistent hepatitis B virus infection among Chinese. However, the mechanisms beyond the genetic variants identified by GWAS located in noncoding regions are largely unknown. To further explore the causal gene of persistent hepatitis B virus (HBV) infection, we used a new approach developed by Gusev and Ko, leveraging expression imputation from large-scale GWAS data by using a small set of individuals with both genotype and gene expression data as a reference panel, to perform a transcriptome-wide association study (TWAS).Based on Genotype-Tissue Expression (GTEx) database, we included 97 individuals with both gene expression data in liver and SNP array data in blood as a reference panel. We first estimated the cis SNP heritability (cis-hg2) for each gene in 97 liver tissues using genome-wide complex trait analysis (GCTA) software, and kept cis-heritable genes for subsequent analysis. Then, we estimated the effect sizes of cis-SNPs on gene expression using genome-wide efficient mixed-model association (GEMMA) algorithm. Using the effect sizes trained from the reference panel, we imputed the gene expression levels for our existing NJMU HEP GWAS cohort (951 persistent hepatitis B virus (HBV) infection patients and 937 controls) and correlated the imputed gene expression values with persistent hepatitis B virus (HBV) infection trait. The cis-hg2 estimate was significantly nonzero for 2588 genes (P<0.05). The average cis-hg2value was 0.438. Using GTEx database as a reference panel. In the training set, After FDR correction, we identified three potentially persistent hepatitis B virus (HBV) infection -associated genes, those genes were located in 6p21.3(HLA-DPA1,PTWAS=2.02×10-7), 3q21.1(PARP9, PTWAS=2.2×10-4) and 22q11.21 (TMEM191A, PTWAS= 3.8×10-4)respectively. 6p21.3 and 22q11.21 as our previous reported. 3q21.1 was a novel region. Citation Format: Jing Han, Jing Ni, Meng Zhu, Jin Guang Fu, Zhi Bin Hu. Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-176.