A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia
Jingjing Zhang1
Qingrong Zhang1
Wenyan Hu1
Yuxuan Liang1
Deke Jiang2
Haitao Chen1
1.School of Public Health(Shenzhen),Sun Yat-sen University,Guangzhou,Guangdong,P.R.China;School of Public Health(Shenzhen),Shenzhen campus of Sun Yat-sen University,Shenzhen,Guangdong,P.R.China2.Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,P.R.China
摘要：Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibility genes underlying these associa-tions largely remain unclear.To identify novel candidate genes for HCC,we conducted liver single-tissue and cross-tissue transcrip-tome-wide association studies(TWASs)in two populations of East Asia.
Methods:GWAS summary statistics of 2,514 subjects(1,161 HCC cases and 1,353 controls)from the Chinese Qidong cohort and 161,323 subjects(2,122 HCC cases and 159,201 controls)from the BioBank Japan project were used to conduct TWAS analysis.The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC.TWAS identified genes were further annotated by Metascape,UALCAN,GEPIA2,and DepMap.
Results:We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction.Of these,13 genes were located in novel regions.Besides,we found 83 genes overlapped in the Chinese and Japanese cohorts with P<0.05,of which,three genes(NUAK2,HLA-DQA1,and ATP6V1G2)were discerned by both single-tissue and cross-tissue TWAS approaches.Among the genes identified through TWAS,a significant proportion of them exhibit a credible role in HCC biology,such as FAM96B,HSPA5,POLRMT,MPHOSPH10,and RABL2A.HLA-DQA1,NUAK2,and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.
Conclusions:Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.
机标关键词：associationeastgenesstudyasiacarcinomahepatocellularidentified
论文发表日期：2024-08-30
在线出版日期：2026-07-17（本平台首次上网日期，不代表文献的发表时间）
页数：11( 386-396 )
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