TY - JOUR
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
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
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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U2 - 10.1038/s41588-018-0336-0
DO - 10.1038/s41588-018-0336-0
M3 - Article
C2 - 30692682
AN - SCOPUS:85060791597
SN - 1061-4036
VL - 51
SP - 470
EP - 480
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -