PLoS Genetics (Jan 2012)

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
https://doi.org/10.1371/journal.pgen.1002791
Journal volume & issue
Vol. 8, no. 7
p. e1002791

Abstract

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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.