Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis

Nao Nishida, Jun Ohashi, Seik Soon Khor, Masaya Sugiyama, Takayo Tsuchiura, Hiromi Sawai, Keisuke Hino, Masao Honda, Shuichi Kaneko, Hiroshi Yatsuhashi, Osamu Yokosuka, Kazuhiko Koike, Masayuki Kurosaki, Namiki Izumi, Masaaki Korenaga, Jong Hon Kang, Eiji Tanaka, Akinobu Taketomi, Yuichiro Eguchi, Naoya SakamotoKazuhide Yamamoto, Akihiro Tamori, Isao Sakaida, Shuhei Hige, Yoshito Itoh, Satoshi Mochida, Eiji Mita, Yasuhiro Takikawa, Tatsuya Ide, Yoichi Hiasa, Hiroto Kojima, Ken Yamamoto, Minoru Nakamura, Hiroh Saji, Takehiko Sasazuki, Tatsuya Kanto, Katsushi Tokunaga, Masashi Mizokami

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Abstract

Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1∗06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 × 10-18) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1∗09:01, and ∗04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1∗15:02-DQB1∗06:01 and DRB1∗13:02-DQB1∗06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region.

Original languageEnglish
Article number24767
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Apr 19 2016

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Chronic Hepatitis B
Alleles
Single Nucleotide Polymorphism
Infection
Genome-Wide Association Study
Haplotypes
HLA-DP Antigens
HLA-C Antigens
HLA-DQ Antigens
HLA-A Antigens
Linkage Disequilibrium
HLA-DR Antigens
Genome
Population
HLA-DPB1 antigen

All Science Journal Classification (ASJC) codes

  • General

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Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis. / Nishida, Nao; Ohashi, Jun; Khor, Seik Soon; Sugiyama, Masaya; Tsuchiura, Takayo; Sawai, Hiromi; Hino, Keisuke; Honda, Masao; Kaneko, Shuichi; Yatsuhashi, Hiroshi; Yokosuka, Osamu; Koike, Kazuhiko; Kurosaki, Masayuki; Izumi, Namiki; Korenaga, Masaaki; Kang, Jong Hon; Tanaka, Eiji; Taketomi, Akinobu; Eguchi, Yuichiro; Sakamoto, Naoya; Yamamoto, Kazuhide; Tamori, Akihiro; Sakaida, Isao; Hige, Shuhei; Itoh, Yoshito; Mochida, Satoshi; Mita, Eiji; Takikawa, Yasuhiro; Ide, Tatsuya; Hiasa, Yoichi; Kojima, Hiroto; Yamamoto, Ken; Nakamura, Minoru; Saji, Hiroh; Sasazuki, Takehiko; Kanto, Tatsuya; Tokunaga, Katsushi; Mizokami, Masashi.

In: Scientific reports, Vol. 6, 24767, 19.04.2016.

Research output: Contribution to journalArticle

Nishida, N, Ohashi, J, Khor, SS, Sugiyama, M, Tsuchiura, T, Sawai, H, Hino, K, Honda, M, Kaneko, S, Yatsuhashi, H, Yokosuka, O, Koike, K, Kurosaki, M, Izumi, N, Korenaga, M, Kang, JH, Tanaka, E, Taketomi, A, Eguchi, Y, Sakamoto, N, Yamamoto, K, Tamori, A, Sakaida, I, Hige, S, Itoh, Y, Mochida, S, Mita, E, Takikawa, Y, Ide, T, Hiasa, Y, Kojima, H, Yamamoto, K, Nakamura, M, Saji, H, Sasazuki, T, Kanto, T, Tokunaga, K & Mizokami, M 2016, 'Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis', Scientific reports, vol. 6, 24767. https://doi.org/10.1038/srep24767
Nishida, Nao ; Ohashi, Jun ; Khor, Seik Soon ; Sugiyama, Masaya ; Tsuchiura, Takayo ; Sawai, Hiromi ; Hino, Keisuke ; Honda, Masao ; Kaneko, Shuichi ; Yatsuhashi, Hiroshi ; Yokosuka, Osamu ; Koike, Kazuhiko ; Kurosaki, Masayuki ; Izumi, Namiki ; Korenaga, Masaaki ; Kang, Jong Hon ; Tanaka, Eiji ; Taketomi, Akinobu ; Eguchi, Yuichiro ; Sakamoto, Naoya ; Yamamoto, Kazuhide ; Tamori, Akihiro ; Sakaida, Isao ; Hige, Shuhei ; Itoh, Yoshito ; Mochida, Satoshi ; Mita, Eiji ; Takikawa, Yasuhiro ; Ide, Tatsuya ; Hiasa, Yoichi ; Kojima, Hiroto ; Yamamoto, Ken ; Nakamura, Minoru ; Saji, Hiroh ; Sasazuki, Takehiko ; Kanto, Tatsuya ; Tokunaga, Katsushi ; Mizokami, Masashi. / Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis. In: Scientific reports. 2016 ; Vol. 6.
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abstract = "Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1∗06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 × 10-18) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1∗09:01, and ∗04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1∗15:02-DQB1∗06:01 and DRB1∗13:02-DQB1∗06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region.",
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AU - Nishida, Nao

AU - Ohashi, Jun

AU - Khor, Seik Soon

AU - Sugiyama, Masaya

AU - Tsuchiura, Takayo

AU - Sawai, Hiromi

AU - Hino, Keisuke

AU - Honda, Masao

AU - Kaneko, Shuichi

AU - Yatsuhashi, Hiroshi

AU - Yokosuka, Osamu

AU - Koike, Kazuhiko

AU - Kurosaki, Masayuki

AU - Izumi, Namiki

AU - Korenaga, Masaaki

AU - Kang, Jong Hon

AU - Tanaka, Eiji

AU - Taketomi, Akinobu

AU - Eguchi, Yuichiro

AU - Sakamoto, Naoya

AU - Yamamoto, Kazuhide

AU - Tamori, Akihiro

AU - Sakaida, Isao

AU - Hige, Shuhei

AU - Itoh, Yoshito

AU - Mochida, Satoshi

AU - Mita, Eiji

AU - Takikawa, Yasuhiro

AU - Ide, Tatsuya

AU - Hiasa, Yoichi

AU - Kojima, Hiroto

AU - Yamamoto, Ken

AU - Nakamura, Minoru

AU - Saji, Hiroh

AU - Sasazuki, Takehiko

AU - Kanto, Tatsuya

AU - Tokunaga, Katsushi

AU - Mizokami, Masashi

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