GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

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

doi:10.1371/journal.pgen.1002791

GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

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 ShiXinchun 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

182 Citations (Scopus)

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.

Original language	English
Article number	e1002791
Journal	PLoS Genetics
Volume	8
Issue number	7
DOIs	https://doi.org/10.1371/journal.pgen.1002791
Publication status	Published - Jul 2012
Externally published	Yes

ASJC Scopus Subject Areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pgen.1002791

Cite this

Li, S., Qian, J., Yang, Y., Zhao, W., Dai, J., Bei, J. X., Foo, J. N., McLaren, P. J., Li, Z., Yang, J., Shen, F., Liu, L., Yang, J., Li, S., Pan, S., Wang, Y., Li, W., Zhai, X., Zhou, B., ... Zhou, W. (2012). GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genetics, 8(7), Article e1002791. https://doi.org/10.1371/journal.pgen.1002791

@article{e356adda297446348e77892764dc4156,

title = "GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers",

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 = "Shengping Li and Ji Qian and Yuan Yang and Wanting Zhao and Juncheng Dai and Bei, {Jin Xin} and Foo, {Jia Nee} and McLaren, {Paul J.} and Zhiqiang Li and Jingmin Yang and Feng Shen and Li Liu and Jiamei Yang and Shuhong Li and Shandong Pan and Yi Wang and Wenjin Li and Xiangjun Zhai and Boping Zhou and Lehua Shi and Xinchun Chen and Minjie Chu and Yiqun Yan and Jun Wang and Shuqun Cheng and Jiawei Shen and Weihua Jia and Jibin Liu and Jiahe Yang and Zujia Wen and Aijun Li and Ying Zhang and Guoliang Zhang and Xianrong Luo and Hongbo Qin and Minshan Chen and Hua Wang and Li Jin and Dongxin Lin and Hongbing Shen and Lin He and {de Bakker}, {Paul I.W.} and Hongyang Wang and Zeng, {Yi Xin} and Mengchao Wu and Zhibin Hu and Yongyong Shi and Jianjun Liu and Weiping Zhou",

year = "2012",

month = jul,

doi = "10.1371/journal.pgen.1002791",

language = "English",

volume = "8",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "7",

}

Li, S, Qian, J, Yang, Y, Zhao, W, Dai, J, Bei, JX, Foo, JN, McLaren, PJ, Li, Z, Yang, J, Shen, F, Liu, L, Yang, J, Li, S, Pan, S, Wang, Y, Li, W, Zhai, X, Zhou, B, Shi, L, Chen, X, Chu, M, Yan, Y, Wang, J, Cheng, S, Shen, J, Jia, W, Liu, J, Yang, J, Wen, Z, Li, A, Zhang, Y, Zhang, G, Luo, X, Qin, H, Chen, M, Wang, H, Jin, L, Lin, D, Shen, H, He, L, de Bakker, PIW, Wang, H, Zeng, YX, Wu, M, Hu, Z, Shi, Y, Liu, J & Zhou, W 2012, 'GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers', PLoS Genetics, vol. 8, no. 7, e1002791. https://doi.org/10.1371/journal.pgen.1002791

TY - JOUR

T1 - GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

AU - Li, Shengping

AU - Qian, Ji

AU - Yang, Yuan

AU - Zhao, Wanting

AU - Dai, Juncheng

AU - Bei, Jin Xin

AU - Foo, Jia Nee

AU - McLaren, Paul J.

AU - Li, Zhiqiang

AU - Yang, Jingmin

AU - Shen, Feng

AU - Liu, Li

AU - Yang, Jiamei

AU - Li, Shuhong

AU - Pan, Shandong

AU - Wang, Yi

AU - Li, Wenjin

AU - Zhai, Xiangjun

AU - Zhou, Boping

AU - Shi, Lehua

AU - Chen, Xinchun

AU - Chu, Minjie

AU - Yan, Yiqun

AU - Wang, Jun

AU - Cheng, Shuqun

AU - Shen, Jiawei

AU - Jia, Weihua

AU - Liu, Jibin

AU - Yang, Jiahe

AU - Wen, Zujia

AU - Li, Aijun

AU - Zhang, Ying

AU - Zhang, Guoliang

AU - Luo, Xianrong

AU - Qin, Hongbo

AU - Chen, Minshan

AU - Wang, Hua

AU - Jin, Li

AU - Lin, Dongxin

AU - Shen, Hongbing

AU - He, Lin

AU - de Bakker, Paul I.W.

AU - Wang, Hongyang

AU - Zeng, Yi Xin

AU - Wu, Mengchao

AU - Hu, Zhibin

AU - Shi, Yongyong

AU - Liu, Jianjun

AU - Zhou, Weiping

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864621505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864621505&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1002791

DO - 10.1371/journal.pgen.1002791

M3 - Article

C2 - 22807686

AN - SCOPUS:84864621505

SN - 1553-7390

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

IS - 7

M1 - e1002791

ER -

GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

Abstract

ASJC Scopus Subject Areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this