Author
Listed:
- Shengping Li
- Ji Qian
- Yuan Yang
- Wanting Zhao
- Juncheng Dai
- Jin-Xin Bei
- Jia Nee Foo
- Paul J McLaren
- Zhiqiang Li
- Jingmin Yang
- Feng Shen
- Li Liu
- Jiamei Yang
- Shuhong Li
- Shandong Pan
- Yi Wang
- Wenjin Li
- Xiangjun Zhai
- Boping Zhou
- Lehua Shi
- Xinchun Chen
- Minjie Chu
- Yiqun Yan
- Jun Wang
- Shuqun Cheng
- Jiawei Shen
- Weihua Jia
- Jibin Liu
- Jiahe Yang
- Zujia Wen
- Aijun Li
- Ying Zhang
- Guoliang Zhang
- Xianrong Luo
- Hongbo Qin
- Minshan Chen
- Hua Wang
- Li Jin
- Dongxin Lin
- Hongbing Shen
- Lin He
- Paul I W de Bakker
- Hongyang Wang
- Yi-Xin Zeng
- Mengchao Wu
- Zhibin Hu
- Yongyong Shi
- Jianjun Liu
- Weiping Zhou
Abstract
Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10−19) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10−8), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10−4; rs455804: OR = 0.84, P = 6.92×10−3). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC. Author Summary: Previous studies strongly suggest the importance of genetic susceptibility for hepatocellular carcinoma (HCC). However, the studies about genetic etiology on HBV–related HCC were limited. Our genome-wide association study included 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers for the discovery analysis. 2,112 HBV–positive HCC cases and 2,208 HBV carriers (the initial validation), and 1,021 cases and 1,491 HBV carriers (the second validation), were then analyzed for validation. The fourth independent samples of 1,298 cases and 1,026 controls were analyzed as replication. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 and rs455804 (GRIK1) on 21q21.3. HLA-DRB1 molecules play an important role in chronic HBV infection and progression to HCC. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC.
Suggested Citation
Shengping Li & Ji Qian & Yuan Yang & Wanting Zhao & Juncheng Dai & Jin-Xin Bei & Jia Nee Foo & Paul J McLaren & Zhiqiang Li & Jingmin Yang & Feng Shen & Li Liu & Jiamei Yang & Shuhong Li & Shandong Pa, 2012.
"GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers,"
PLOS Genetics, Public Library of Science, vol. 8(7), pages 1-8, July.
Handle:
RePEc:plo:pgen00:1002791
DOI: 10.1371/journal.pgen.1002791
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Citations
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Cited by:
- Yun Liao & Bei Cai & Yi Li & Jie Chen & Chuanmin Tao & Hengjian Huang & Lanlan Wang, 2014.
"Association of HLA-DP/DQ and STAT4 Polymorphisms with HBV Infection Outcomes and a Mini Meta-Analysis,"
PLOS ONE, Public Library of Science, vol. 9(11), pages 1-9, November.
- Yifang Han & Rui Pu & Xue Han & Jun Zhao & Yuwei Zhang & Qi Zhang & Jianhua Yin & Jiaxin Xie & Qiuxia Shen & Yang Deng & Yibo Ding & Weiping Li & Juhong Li & Hongwei Zhang & Guangwen Cao, 2013.
"Associations of pri-miR-34b/c and pre-miR-196a2 Polymorphisms and Their Multiplicative Interactions with Hepatitis B Virus Mutations with Hepatocellular Carcinoma Risk,"
PLOS ONE, Public Library of Science, vol. 8(3), pages 1-9, March.
- Zhi-Chao Wang & Qiang Gao & Jie-Yi Shi & Liu-Xiao Yang & Jian Zhou & Xiao-Ying Wang & Ying-Hong Shi & Ai-Wu Ke & Guo-Ming Shi & Zhen-Bin Ding & Zhi Dai & Shuang-Jian Qiu & Jia Fan, 2013.
"Genetic Polymorphism of the Kinesin-Like Protein KIF1B Gene and the Risk of Hepatocellular Carcinoma,"
PLOS ONE, Public Library of Science, vol. 8(4), pages 1-6, April.
- Nao Nishida & Hiromi Sawai & Koichi Kashiwase & Mutsuhiko Minami & Masaya Sugiyama & Wai-Kay Seto & Man-Fung Yuen & Nawarat Posuwan & Yong Poovorawan & Sang Hoon Ahn & Kwang-Hyub Han & Kentaro Matsuur, 2014.
"New Susceptibility and Resistance HLA-DP Alleles to HBV-Related Diseases Identified by a Trans-Ethnic Association Study in Asia,"
PLOS ONE, Public Library of Science, vol. 9(2), pages 1-7, February.
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