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New loci associated with chronic hepatitis B virus infection in Han Chinese

Abstract

Chronic hepatitis B virus (HBV) infection is a challenging global health problem. To identify genetic loci involved in chronic HBV infection, we designed a three-phase genome-wide association study in Han Chinese populations. The discovery phase included 951 HBV carriers (cases) and 937 individuals who had naturally cleared HBV infection (controls) and was followed by independent replications with a total of 2,248 cases and 3,051 controls and additional replications with 1,982 HBV carriers and 2,622 controls from the general population. We identified two new loci associated with chronic HBV infection: rs3130542 at 6p21.33 (near HLA-C, odds ratio (OR) = 1.33, P = 9.49 × 10−14) and rs4821116 at 22q11.21 (in UBE2L3, OR = 0.82, P = 1.71 × 10−12). Additionally, we replicated the previously identified associations of HLA-DP and HLA-DQ variants at 6p21.32 with chronic HBV infection. These findings highlight the importance of HLA-C and UBE2L3 in the clearance of HBV infection in addition to HLA-DP and HLA-DQ.

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Figure 1: Regional plots of the three marker SNPs associated with chronic HBV infection.

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Acknowledgements

The authors thank all study subjects, research staff and students who participated in this work and Z. Wang (US National Cancer Institute) for statistical help with imputation. This work was funded by the National Key Basic Research Program (2013CB911400), the project supported by the National Science Foundation for Distinguished Young Scholars of China (81225020), the project supported by the State Key Program of National Natural Science of China (81230067), the Foundation for the Program for New Century Excellent Talents in University (NCET-10-0178), the Author of National Excellent Doctoral Dissertation (201081), the National Natural Science Foundation of China (30800946 and 81072344), the State Key Infectious Disease Project of China (2012ZX10002010 and 2012ZX10002016), the National Major Science & Technology Project (2011ZX10004-902), the National Science Fund for Creative Research Groups (30921006), the National Key Basic Research Program (2013CB910304), a China National High-Tech Research and Development Program grant (2012AA02A515), the Foundation for Distinguished Young Scholars of Jiangsu Province (BK2012042 and BK20130042) and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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Contributions

H.S. and Z.H. directed the study, obtained financial support and were responsible for study design, interpretation of the results and manuscript writing together with W.Z. and Y.S. Z.H. performed overall project management along with Y.L., G.J. and X.Z. and drafted the initial manuscript. J.D. performed statistical analyses along with Y.L. Y.L., M. Chu, J.W., Y.H. and K.X. were responsible for sample processing and managing the genotyping data. Y.Y. and Y.H. were responsible for subject recruitment and sample preparation for the Shanghai samples. X.Z., L.Z., G.D., Q.W., H.Y. and M. Cao were responsible for subject recruitment and sample preparation for the Zhangjiagang and Changzhou samples. X.Z., Y.Z. and J.W. were responsible for subject recruitment and sample preparation for the Taizhou samples. Jibin Liu, L.L. and K.X. were responsible for subject recruitment and sample preparation for the Nantong samples. L.W., G.Z. and Y.W. were responsible for subject recruitment and sample preparation for the Beijing samples. W.J., S.L. and J. Lu were responsible for subject recruitment and sample preparation for the Guangdong samples. Jianjun Liu provided technical and material support. All authors approved the final manuscript.

Corresponding authors

Correspondence to Zhibin Hu, Yongyong Shi, Weiping Zhou or Hongbing Shen.

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The authors declare no competing financial interests.

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Hu, Z., Liu, Y., Zhai, X. et al. New loci associated with chronic hepatitis B virus infection in Han Chinese. Nat Genet 45, 1499–1503 (2013). https://doi.org/10.1038/ng.2809

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