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

Fusheng Zhou, Hongzhi Cao, Xianbo Zuo, Tao Zhang, Xiaoguang Zhang, Xiaomin Liu, Ricong Xu, Gang Chen, Yuanwei Zhang, Xiaodong Zheng, Xin Jin, Jinping Gao, Junpu Mei, Yujun Sheng, Qibin Li, Bo Liang, Juan Shen, Changbing Shen, Hui Jiang, Caihong Zhu, Xing Fan, Fengping Xu, Min Yue, Xianyong Yin, Chen Ye, Cuicui Zhang, Xiao Liu, Liang Yu, Jinghua Wu, Mengyun Chen, Xuehan Zhuang, Lili Tang, Haojing Shao, Longmao Wu, Jian Li, Yu Xu, Yijie Zhang, Suli Zhao, Yu Wang, Ge Li, Hanshi Xu, Lei Zeng, Jianan Wang, Mingzhou Bai, Yanling Chen, Wei Chen, Tian Kang, Yanyan Wu, Xun Xu, Zhengwei Zhu, Yong Cui, Zaixing Wang, Chunjun Yang, Peiguang Wang, Leihong Xiang, Xiang Chen, Anping Zhang, Xinghua Gao, Furen Zhang, Jinhua Xu, Min Zheng, Jie Zheng, Jianzhong Zhang, Xueqing Yu, Yingrui Li, Sen Yang, Huanming Yang, Jian Wang, Jianjun Liu, Lennart Hammarström, Liangdan Sun, Jun Wang, Xuejun Zhang

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.