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

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