Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population

Jun Hirata, Kazuyoshi Hosomichi, Saori Sakaue, Masahiro Kanai, Hirofumi Nakaoka, Kazuyoshi Ishigaki, Ken Suzuki, Masato Akiyama, Toshihiro Kishikawa, Kotaro Ogawa, Tatsuo Masuda, Kenichi Yamamoto, Makoto Hirata, Koichi Matsuda, Yukihide Momozawa, Ituro Inoue, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada

研究成果: Article

1 引用 (Scopus)

抄録

To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype–phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.

元の言語English
ページ(範囲)470-480
ページ数11
ジャーナルNature Genetics
51
発行部数3
DOI
出版物ステータスPublished - 01-03-2019

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HLA Antigens
Phenotype
Population
Genes
Genome-Wide Association Study
Linkage Disequilibrium
Major Histocompatibility Complex
Nucleotides
Alleles
Genome

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Hirata, J., Hosomichi, K., Sakaue, S., Kanai, M., Nakaoka, H., Ishigaki, K., ... Okada, Y. (2019). Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population. Nature Genetics, 51(3), 470-480. https://doi.org/10.1038/s41588-018-0336-0
Hirata, Jun ; Hosomichi, Kazuyoshi ; Sakaue, Saori ; Kanai, Masahiro ; Nakaoka, Hirofumi ; Ishigaki, Kazuyoshi ; Suzuki, Ken ; Akiyama, Masato ; Kishikawa, Toshihiro ; Ogawa, Kotaro ; Masuda, Tatsuo ; Yamamoto, Kenichi ; Hirata, Makoto ; Matsuda, Koichi ; Momozawa, Yukihide ; Inoue, Ituro ; Kubo, Michiaki ; Kamatani, Yoichiro ; Okada, Yukinori. / Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population. :: Nature Genetics. 2019 ; 巻 51, 番号 3. pp. 470-480.
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abstract = "To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype–phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.",
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Hirata, J, Hosomichi, K, Sakaue, S, Kanai, M, Nakaoka, H, Ishigaki, K, Suzuki, K, Akiyama, M, Kishikawa, T, Ogawa, K, Masuda, T, Yamamoto, K, Hirata, M, Matsuda, K, Momozawa, Y, Inoue, I, Kubo, M, Kamatani, Y & Okada, Y 2019, 'Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population', Nature Genetics, 巻. 51, 番号 3, pp. 470-480. https://doi.org/10.1038/s41588-018-0336-0

Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population. / Hirata, Jun; Hosomichi, Kazuyoshi; Sakaue, Saori; Kanai, Masahiro; Nakaoka, Hirofumi; Ishigaki, Kazuyoshi; Suzuki, Ken; Akiyama, Masato; Kishikawa, Toshihiro; Ogawa, Kotaro; Masuda, Tatsuo; Yamamoto, Kenichi; Hirata, Makoto; Matsuda, Koichi; Momozawa, Yukihide; Inoue, Ituro; Kubo, Michiaki; Kamatani, Yoichiro; Okada, Yukinori.

:: Nature Genetics, 巻 51, 番号 3, 01.03.2019, p. 470-480.

研究成果: Article

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T1 - Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population

AU - Hirata, Jun

AU - Hosomichi, Kazuyoshi

AU - Sakaue, Saori

AU - Kanai, Masahiro

AU - Nakaoka, Hirofumi

AU - Ishigaki, Kazuyoshi

AU - Suzuki, Ken

AU - Akiyama, Masato

AU - Kishikawa, Toshihiro

AU - Ogawa, Kotaro

AU - Masuda, Tatsuo

AU - Yamamoto, Kenichi

AU - Hirata, Makoto

AU - Matsuda, Koichi

AU - Momozawa, Yukihide

AU - Inoue, Ituro

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

AU - Okada, Yukinori

PY - 2019/3/1

Y1 - 2019/3/1

N2 - To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype–phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.

AB - To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype–phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.

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