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

被引：76

作者：

Hirata, Jun ^{[1
,2
]}

Hosomichi, Kazuyoshi ^{[3
]}

Sakaue, Saori ^{[1
,4
,5
]}

Kanai, Masahiro ^{[1
,4
,6
]}

Nakaoka, Hirofumi ^{[7
]}

Ishigaki, Kazuyoshi ^{[4
]}

Suzukil, Ken ^{[1
,4
,8
]}

Akiyama, Masato ^{[4
,9
]}

Kishikawa, Toshihiro ^{[1
,10
]}

Ogawa, Kotaro ^{[1
,11
]}

Masuda, Tatsuo ^{[1
,12
]}

Yamamoto, Kenichi ^{[1
,13
]}

Hirata, Makoto ^{[14
]}

Matsuda, Koichi ^{[15
]}

Momozawa, Yukihide ^{[16
]}

Inoue, Ituro ^{[7
]}

Kubo, Michiaki ^{[17
]}

Kamatani, Yoichiro ^{[4
,18
]}

Okada, Yukinori ^{[1
,4
,19
]}

机构：

[1] Osaka Univ, Dept Stat Genet, Grad Sch Med, Suita, Osaka, Japan

[2] Teijin Pharma Ltd, Pharmaceut Discovery Res Labs, Hino, Tokyo, Japan

[3] Kanazawa Univ, Grad Sch Adv Prevent Med Sci, Dept Bioinformat & Genom, Kanazawa, Ishikawa, Japan

[4] RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[5] Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan

[6] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA

[7] Natl Inst Genet, Div Human Genet, Shizuoka, Japan

[8] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan

[9] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka, Japan

[10] Osaka Univ, Grad Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Osaka, Japan

[11] Osaka Univ, Dept Neurol, Grad Sch Med, Osaka, Japan

[12] Osaka Univ, Dept Obstet & Gynecol, Grad Sch Med, Osaka, Japan

[13] Osaka Univ, Dept Pediat, Grad Sch Med, Osaka, Japan

[14] Univ Tokyo, Inst Med Sci, Lab Genome Technol, Tokyo, Japan

[15] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Tokyo, Japan

[16] RIKEN, Lab Genotyping Dev, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[17] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[18] Kyoto McGill Int Collaborat Sch Genom Med, Sakyo Ku, Kyoto, Japan

[19] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan

来源：

NATURE GENETICS | 2019年 / 51卷 / 03期

基金：

日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; HLA; RISK; MHC; PROJECT; SUSCEPTIBILITY; HERITABILITY; EXPRESSION; PSORIASIS; VARIANTS;

D O I：

10.1038/s41588-018-0336-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：470 / +

页数：13

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