title: Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease.
abstract: 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.
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|iCarbonX, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaomin
authors.identifier: 0000-0003-2155-3627
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, China.
authors.forename: Ricong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Gao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Junpu
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fan
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fengping
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ye
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Mengyun
authors.initials: M
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xuehan
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Haojing
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Longmao
authors.initials: L
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Suli
authors.initials: S
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Bai
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Kang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Chunjun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Peiguang
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Leihong
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Anping
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Gao
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Furen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Huashan Hospital and Collaborative Innovation Center of Complex and Severe Skin Disease, Fudan University, Shanghai, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, Peking University People's Hospital, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|iCarbonX, Shenzhen, China.|Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|James D. Watson Institute of Genome Sciences, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|iCarbonX, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.|Princess Al-Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.|Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China.|Department of Medicine, University of Hong Kong, Hong Kong, China.|State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China.|Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.|Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, China.|Department of Dermatology, Huashan Hospital and Collaborative Innovation Center of Complex and Severe Skin Disease, Fudan University, Shanghai, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics*; D000071797:Butyrophilins / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics*
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen