Trans-ethnic genome-wide association study of severe COVID-19

Peng Wu; Lin Ding; Xiaodong Li; Siyang Liu; Fanjun Cheng; Qing He; Mingzhong Xiao; Ping Wu; Hongyan Hou; Minghui Jiang; Pinpin Long; Hao Wang; Linlin Liu; Minghan Qu; Xian Shi; Qin Jiang; Tingting Mo; Wencheng Ding; Yu Fu; Shi Han; Xixiang Huo; Yingchun Zeng; Yana Zhou; Qing Zhang; Jia Ke; Xi Xu; Wei Ni; Zuoyu Shao; Jingzhi Wang; Panhong Liu; Zilong Li; Yan Jin; Fang Zheng; Fang Wang; Lei Liu; Wending Li; Kang Liu; Rong Peng; Xuedan Xu; Yuhui Lin; Hui Gao; Limei Shi; Ziyue Geng; Xuanwen Mu; Yu Yan; Kai Wang; Degang Wu; Xingjie Hao; Shanshan Cheng; Gaokun Qiu; Huan Guo; Kezhen Li; Gang Chen; Ziyong Sun; Xihong Lin; Xin Jin; Feng Wang; Chaoyang Sun; Chaolong Wang

doi:10.1038/s42003-021-02549-5

Trans-ethnic genome-wide association study of severe COVID-19

Commun Biol. 2021 Aug 31;4(1):1034. doi: 10.1038/s42003-021-02549-5.

Authors

Peng Wu^#^{1

2}, Lin Ding^#^{3

4}, Xiaodong Li^#^{5

6}, Siyang Liu^#⁷, Fanjun Cheng^#⁸, Qing He^#⁹, Mingzhong Xiao^{5

6}, Ping Wu^{1

2}, Hongyan Hou^{2

10}, Minghui Jiang^{3

4}, Pinpin Long^{4

11}, Hao Wang^{4

11}, Linlin Liu¹², Minghan Qu^{3

4}, Xian Shi^{3

4}, Qin Jiang^{4

11}, Tingting Mo^{4

11}, Wencheng Ding^{1

2}, Yu Fu^{1

2}, Shi Han¹², Xixiang Huo¹², Yingchun Zeng¹², Yana Zhou^{5

6}, Qing Zhang^{5

6}, Jia Ke^{5

6}, Xi Xu^{5

6}, Wei Ni^{5

6}, Zuoyu Shao^{5

6}, Jingzhi Wang^{5

6}, Panhong Liu¹³, Zilong Li¹³, Yan Jin¹⁴, Fang Zheng¹⁵, Fang Wang⁹, Lei Liu⁹, Wending Li^{4

11}, Kang Liu^{4

11}, Rong Peng^{4

11}, Xuedan Xu^{4

11}, Yuhui Lin^{4

11}, Hui Gao^{4

11}, Limei Shi^{4

11}, Ziyue Geng^{4

11}, Xuanwen Mu^{4

11}, Yu Yan^{3

4}, Kai Wang^{3

4}, Degang Wu^{3

4}, Xingjie Hao^{3

4}, Shanshan Cheng^{3

4}, Gaokun Qiu^{4

11}, Huan Guo^{4

11}, Kezhen Li^{1

2}, Gang Chen^{1

2}, Ziyong Sun^{2

10}, Xihong Lin^{16

17

18}, Xin Jin¹⁹, Feng Wang^{20

21}, Chaoyang Sun^{22

23}, Chaolong Wang^{24

25

26}

Affiliations

¹ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² National Medical Center for Major Public Health Events, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Hepatic Disease Institute, Hubei Key Laboratory of Theoretical and Applied Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
⁶ Hubei Provincial Academy of Traditional Chinese Medicine, Wuhan, China.
⁷ School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China.
⁸ Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁹ The Third People's Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
¹⁰ Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹¹ Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹² Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
¹³ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
¹⁴ Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁵ Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁶ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁷ Department of Statistics, Harvard University, Cambridge, MA, USA.
¹⁸ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁹ School of Medicine, South China University of Technology, Guangzhou, China. jinxin@genomics.cn.
²⁰ National Medical Center for Major Public Health Events, Huazhong University of Science and Technology, Wuhan, China. fengwang@tjh.tjmu.edu.cn.
²¹ Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. fengwang@tjh.tjmu.edu.cn.
²² Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. suncydoctor@gmail.com.
²³ National Medical Center for Major Public Health Events, Huazhong University of Science and Technology, Wuhan, China. suncydoctor@gmail.com.
²⁴ National Medical Center for Major Public Health Events, Huazhong University of Science and Technology, Wuhan, China. chaolong@hust.edu.cn.
²⁵ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. chaolong@hust.edu.cn.
²⁶ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. chaolong@hust.edu.cn.

^# Contributed equally.

Abstract

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10^-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10^-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10^-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 / ethnology*
COVID-19 / genetics*
Ethnicity / genetics*
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study*
Humans
Introns / genetics
Polymorphism, Single Nucleotide