A genome-wide association study identified new variants associated with the risk of chronic hepatitis B

Yoon Jun Kim; Hwi Young Kim; Jeong Hoon Lee; Su Jong Yu; Jung Hwan Yoon; Hyo Suk Lee; Chung Yong Kim; Jae Youn Cheong; Sung Won Cho; Neung Hwa Park; Byung Lae Park; Seok Namgoong; Lyoung Kim; Hyo Hyun Sub Cheong; Hyoung Doo Shin

doi:10.1093/hmg/ddt266

A genome-wide association study identified new variants associated with the risk of chronic hepatitis B

Yoon Jun Kim, Hwi Young Kim, Jeong Hoon Lee, Su Jong Yu, Jung Hwan Yoon, Hyo Suk Lee, Chung Yong Kim, Jae Youn Cheong, Sung Won Cho, Neung Hwa Park, Byung Lae Park, Seok Namgoong, Lyoung Kim, Hyo Hyun Sub Cheong, Hyoung Doo Shin

Department of Internal Medicine

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

98 Scopus citations

Abstract

Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) andhepatocellular carcinoma (HCC). Recently, several genome-wide association studies(GWASs) ofCHBidentified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e.g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 × 10^-13) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 × 10^-18). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. Conclusion: TheGWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.

Original language	English
Article number	ddt266
Pages (from-to)	4233-4238
Number of pages	6
Journal	Human Molecular Genetics
Volume	22
Issue number	20
DOIs	https://doi.org/10.1093/hmg/ddt266
State	Published - Oct 2013

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (No. 2011-0004453); a Sogang University Research Grant for 2011 (SRF-201114006.01); the SNUH Research Fund (03-2012-021); the SK Telecom Research Fund (3420130070); the Basic Research Laboratory Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (2010-0001200) and a grant from the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No. A101023).

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Kim, Y. J., Kim, H. Y., Lee, J. H., Yu, S. J., Yoon, J. H., Lee, H. S., Kim, C. Y., Cheong, J. Y., Cho, S. W., Park, N. H., Park, B. L., Namgoong, S., Kim, L., Cheong, H. H. S., & Shin, H. D. (2013). A genome-wide association study identified new variants associated with the risk of chronic hepatitis B. Human Molecular Genetics, 22(20), 4233-4238. Article ddt266. https://doi.org/10.1093/hmg/ddt266

@article{b3811befa38945baac0ccf565d8ee21d,

title = "A genome-wide association study identified new variants associated with the risk of chronic hepatitis B",

abstract = "Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) andhepatocellular carcinoma (HCC). Recently, several genome-wide association studies(GWASs) ofCHBidentified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e.g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 × 10-13) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 × 10-18). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. Conclusion: TheGWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.",

author = "Kim, {Yoon Jun} and Kim, {Hwi Young} and Lee, {Jeong Hoon} and Yu, {Su Jong} and Yoon, {Jung Hwan} and Lee, {Hyo Suk} and Kim, {Chung Yong} and Cheong, {Jae Youn} and Cho, {Sung Won} and Park, {Neung Hwa} and Park, {Byung Lae} and Seok Namgoong and Lyoung Kim and Cheong, {Hyo Hyun Sub} and Shin, {Hyoung Doo}",

note = "Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (No. 2011-0004453); a Sogang University Research Grant for 2011 (SRF-201114006.01); the SNUH Research Fund (03-2012-021); the SK Telecom Research Fund (3420130070); the Basic Research Laboratory Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (2010-0001200) and a grant from the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No. A101023).",

year = "2013",

month = oct,

doi = "10.1093/hmg/ddt266",

language = "English",

volume = "22",

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T1 - A genome-wide association study identified new variants associated with the risk of chronic hepatitis B

AU - Kim, Yoon Jun

AU - Kim, Hwi Young

AU - Lee, Jeong Hoon

AU - Yu, Su Jong

AU - Yoon, Jung Hwan

AU - Lee, Hyo Suk

AU - Kim, Chung Yong

AU - Cheong, Jae Youn

AU - Cho, Sung Won

AU - Park, Neung Hwa

AU - Park, Byung Lae

AU - Namgoong, Seok

AU - Kim, Lyoung

AU - Cheong, Hyo Hyun Sub

AU - Shin, Hyoung Doo

N1 - Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (No. 2011-0004453); a Sogang University Research Grant for 2011 (SRF-201114006.01); the SNUH Research Fund (03-2012-021); the SK Telecom Research Fund (3420130070); the Basic Research Laboratory Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (2010-0001200) and a grant from the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No. A101023).

PY - 2013/10

Y1 - 2013/10

N2 - Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) andhepatocellular carcinoma (HCC). Recently, several genome-wide association studies(GWASs) ofCHBidentified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e.g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 × 10-13) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 × 10-18). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. Conclusion: TheGWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.

AB - Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) andhepatocellular carcinoma (HCC). Recently, several genome-wide association studies(GWASs) ofCHBidentified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e.g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 × 10-13) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 × 10-18). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. Conclusion: TheGWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.

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ER -

A genome-wide association study identified new variants associated with the risk of chronic hepatitis B

Abstract

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