Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease

被引：170

作者：

Zhou, Fusheng ^{[1
,2
]}

Cao, Hongzhi ^{[3
,4
,5
]}

Zuo, Xianbo ^{[1
,2
]}

Zhang, Tao ^{[3
]}

Zhang, Xiaoguang ^{[1
,2
]}

Liu, Xiaomin ^{[3
]}

Xu, Ricong ^{[6
]}

Chen, Gang ^{[1
,2
]}

Zhang, Yuanwei ^{[3
,7
]}

Zheng, Xiaodong ^{[1
,2
]}

Jin, Xin ^{[3
]}

Gao, Jinping ^{[1
,2
]}

Mei, Junpu ^{[3
]}

Sheng, Yujun ^{[1
,2
]}

Li, Qibin ^{[3
]}

Liang, Bo ^{[1
,2
]}

Shen, Juan ^{[3
]}

Shen, Changbing ^{[1
,2
]}

Jiang, Hui ^{[3
,5
]}

Zhu, Caihong ^{[1
,2
]}

Fan, Xing ^{[1
,2
]}

Xu, Fengping ^{[3
,5
]}

Yue, Min ^{[1
,2
]}

Yin, Xianyong ^{[1
,2
]}

Ye, Chen ^{[3
]}

Zhang, Cuicui ^{[1
,2
]}

Liu, Xiao ^{[3
,5
]}

Yu, Liang ^{[1
,2
]}

Wu, Jinghua ^{[3
]}

Chen, Mengyun ^{[1
,2
]}

Zhuang, Xuehan ^{[3
]}

Tang, Lili ^{[1
,2
]}

Shao, Haojing ^{[3
]}

Wu, Longmao ^{[1
,2
]}

Li, Jian ^{[3
,5
]}

Xu, Yu ^{[1
,2
]}

Zhang, Yijie ^{[3
]}

Zhao, Suli ^{[1
,2
]}

Wang, Yu ^{[3
]}

Li, Ge ^{[1
,2
]}

Xu, Hanshi ^{[3
]}

Zeng, Lei ^{[1
,2
]}

Wang, Jianan ^{[3
]}

Bai, Mingzhou ^{[4
]}

Chen, Yanling ^{[3
]}

Chen, Wei ^{[3
]}

Kang, Tian ^{[3
]}

Wu, Yanyan ^{[1
,2
]}

Xu, Xun ^{[3
]}

Zhu, Zhengwei ^{[1
,2
]}

机构：

[1] Anhui Med Univ, Minist Educ, Hosp 1, Dept Dermatol, Hefei, Peoples R China

[2] Anhui Med Univ, Minist Educ, Key Lab Dermatol, Hefei, Peoples R China

[3] BGI Shenzhen, Shenzhen, Peoples R China

[4] iCarbonX, Shenzhen, Peoples R China

[5] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[6] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Minist Hlth,Key Lab Nephrol, Guangzhou 510275, Guangdong, Peoples R China

[7] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China

[8] China Japan Friendship Hosp, Dept Dermatol, Beijing, Peoples R China

[9] Anhui Med Univ, Hosp 2, Dept Dermatol, Hefei, Peoples R China

[10] Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China

[11] China Med Univ, Hosp 1, Dept Dermatol, Shenyang 110001, Peoples R China

[12] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan, Peoples R China

[13] Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai 200433, Peoples R China

[14] Fudan Univ, Collaborat Innovat Ctr Complex & Severe Skin Dis, Shanghai 200433, Peoples R China

[15] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Dermatol, Hangzhou 310003, Zhejiang, Peoples R China

[16] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Dermatol, Shanghai, Peoples R China

[17] Peking Univ, Peoples Hosp, Dept Dermatol, Beijing 100871, Peoples R China

[18] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[19] James D Watson Inst Genome Sci, Hangzhou, Zhejiang, Peoples R China

[20] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Stockholm, Sweden

[21] King Abdulaziz Univ, Princess Al Jawhara Albrahim Ctr Excellence Res H, Jeddah 21413, Saudi Arabia

[22] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, Taipa, Macau, Peoples R China

[23] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[24] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE GENETICS | 2016年 / 48卷 / 07期

基金：

中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; HIGH-RESOLUTION HLA; HAN CHINESE; RISK LOCI; VARIANTS; PSORIASIS; HETEROGENEITY; MULTIPLE; EXPLAIN;

D O I：

10.1038/ng.3576

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

引用

页码：740 / +

页数：9

共 54 条

[41] The IPD and IMGT/HLA database: allele variant databases
Robinson, James
Halliwell, Jason A.
Hayhurst, James D.
Flicek, Paul
Parham, Peter
Marsh, Steven G. E.
[J]. NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) : D423 - D431
[42] MutationTaster evaluates disease-causing potential of sequence alterations
Schwarz, Jana Marie
Roedelsperger, Christian
Schuelke, Markus
Seelow, Dominik
[J]. NATURE METHODS, 2010, 7 (08) : 575 - 576
[43] INTERACTION OF MHC CLASS-I MOLECULES WITH THE TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING
SUH, WK
COHENDOYLE, MF
FRUH, K
WANG, K
PETERSON, PA
WILLIAMS, DB
[J]. SCIENCE, 1994, 264 (5163) : 1322 - 1326
[44] A large-scale screen for coding variants predisposing to psoriasis
Tang, Huayang
Jin, Xin
Li, Yang
Jiang, Hui
Tang, Xianfa
Yang, Xu
Cheng, Hui
Qiu, Ying
Chen, Gang
Mei, Junpu
Zhou, Fusheng
Wu, Renhua
Zuo, Xianbo
Zhang, Yong
Zheng, Xiaodong
Cai, Qi
Yin, Xianyong
Quan, Cheng
Shao, Haojing
Cui, Yong
Tian, Fangzhen
Zhao, Xia
Liu, Hong
Xiao, Fengli
Xu, Fengping
Han, Jianwen
Shi, Dongmei
Zhang, Anping
Zhou, Cheng
Li, Qibin
Fan, Xing
Lin, Liya
Tian, Hongqing
Wang, Zaixing
Fu, Huiling
Wang, Fang
Yang, Baoqi
Huang, Shaowei
Liang, Bo
Xie, Xuefeng
Ren, Yunqing
Gu, Qingquan
Wen, Guangdong
Sun, Yulin
Wu, Xueli
Dang, Lin
Xia, Min
Shan, Junjun
Li, Tianhang
Yang, Lin
[J]. NATURE GENETICS, 2014, 46 (01) : 45 - +
[45] Major Histocompatibility Complex Genomics and Human Disease
Trowsdale, John
Knight, Julian C.
[J]. ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 14, 2013, 14 : 301 - 323
[46] The MHC, disease and selection
Trowsdale, John
[J]. IMMUNOLOGY LETTERS, 2011, 137 (1-2) : 1 - 8
[47] ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, Kai
Li, Mingyao
Hakonarson, Hakon
[J]. NUCLEIC ACIDS RESEARCH, 2010, 38 (16) : e164
[48] The NHGRI GWAS Catalog, a curated resource of SNP-trait associations
Welter, Danielle
MacArthur, Jacqueline
Morales, Joannella
Burdett, Tony
Hall, Peggy
Junkins, Heather
Klemm, Alan
Flicek, Paul
Manolio, Teri
Hindorff, Lucia
Parkinson, Helen
[J]. NUCLEIC ACIDS RESEARCH, 2014, 42 (D1) : D1001 - D1006
[49] GCTA: A Tool for Genome-wide Complex Trait Analysis
Yang, Jian
Lee, S. Hong
Goddard, Michael E.
Visscher, Peter M.
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (01) : 76 - 82
[50] Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility
Yin, Xianyong
Low, Hui Qi
Wang, Ling
Li, Yonghong
Ellinghaus, Eva
Han, Jiali
Estivill, Xavier
Sun, Liangdan
Zuo, Xianbo
Shen, Changbing
Zhu, Caihong
Zhang, Anping
Sanchez, Fabio
Padyukov, Leonid
Catanese, Joseph J.
Krueger, Gerald G.
Duffin, Kristina Callis
Mucha, Soeren
Weichenthal, Michael
Weidinger, Stephan
Lieb, Wolfgang
Foo, Jia Nee
Li, Yi
Sim, Karseng
Liany, Herty
Irwan, Ishak
Teo, Yikying
Theng, Colin T. S.
Gupta, Rashmi
Bowcock, Anne
De Jager, Philip L.
Qureshi, Abrar A.
de Bakker, Paul I. W.
Seielstad, Mark
Liao, Wilson
Stahle, Mona
Franke, Andre
Zhang, Xuejun
Liu, Jianjun
[J]. NATURE COMMUNICATIONS, 2015, 6

← 1 2 3 4 5 6 →