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

被引：27

作者：

Wu, Peng ^{[1
,2
]}

Ding, Lin ^{[3
,4
]}

Li, Xiaodong ^{[5
,6
]}

Liu, Siyang ^{[7
]}

Cheng, Fanjun ^{[8
]}

He, Qing ^{[9
]}

Xiao, Mingzhong ^{[5
,6
]}

Wu, Ping ^{[1
,2
]}

Hou, Hongyan ^{[2
,10
]}

Jiang, Minghui ^{[3
,4
]}

Long, Pinpin ^{[4
,11
]}

Wang, Hao ^{[4
,11
]}

Liu, Linlin ^{[12
]}

Qu, Minghan ^{[3
,4
]}

Shi, Xian ^{[3
,4
]}

Jiang, Qin ^{[4
,11
]}

Mo, Tingting ^{[4
,11
]}

Ding, Wencheng ^{[1
,2
]}

Fu, Yu ^{[1
,2
]}

Han, Shi ^{[12
]}

Huo, Xixiang ^{[12
]}

Zeng, Yingchun ^{[12
]}

Zhou, Yana ^{[5
,6
]}

Zhang, Qing ^{[5
,6
]}

Ke, Jia ^{[5
,6
]}

Xu, Xi ^{[5
,6
]}

Ni, Wei ^{[5
,6
]}

Shao, Zuoyu ^{[5
,6
]}

Wang, Jingzhi ^{[5
,6
]}

Liu, Panhong ^{[13
]}

Li, Zilong ^{[13
]}

Jin, Yan ^{[14
]}

Zheng, Fang ^{[15
]}

Wang, Fang ^{[9
]}

Liu, Lei ^{[9
]}

Li, Wending ^{[4
,11
]}

Liu, Kang ^{[4
,11
]}

Peng, Rong ^{[4
,11
]}

Xu, Xuedan ^{[4
,11
]}

Lin, Yuhui ^{[4
,11
]}

Gao, Hui ^{[4
,11
]}

Shi, Limei ^{[4
,11
]}

Geng, Ziyue ^{[4
,11
]}

Mu, Xuanwen ^{[4
,11
]}

Yan, Yu ^{[3
,4
]}

Wang, Kai ^{[3
,4
]}

Wu, Degang ^{[3
,4
]}

Hao, Xingjie ^{[3
,4
]}

Cheng, Shanshan ^{[3
,4
]}

Qiu, Gaokun ^{[4
,11
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, Natl Med Ctr Major Publ Hlth Events, Wuhan, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, Wuhan, Peoples R China

[4] Huazhong Univ Sci & Technol, Tongji Med Coll, State Key Lab Environm Hlth Incubating, Sch Publ Hlth,Minist Educ,Key Lab Environm & Hlth, Wuhan, Peoples R China

[5] Hubei Prov Hosp Tradit Chinese Med, Hepat Dis Inst, Hubei Key Lab Theoret & Appl Res Liver & Kidney T, Wuhan, Peoples R China

[6] Hubei Prov Acad Tradit Chinese Med, Wuhan, Peoples R China

[7] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen, Guangdong, Peoples R China

[8] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Hematol, Wuhan, Peoples R China

[9] Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen, Peoples R China

[10] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Lab Med, Wuhan, Peoples R China

[11] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Peoples R China

[12] Hubei Prov Ctr Dis Control & Prevent, Wuhan, Peoples R China

[13] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China

[14] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Emergency, Wuhan, Peoples R China

[15] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pediat, Wuhan, Peoples R China

[16] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[17] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA

[18] Broad Inst MIT & Harvard, Cambridge, MA USA

[19] South China Univ Technol, Sch Med, Guangzhou, Peoples R China

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

关键词：

GENE-EXPRESSION; BLOOD-GROUP; MEF2; TRANSCRIPTION; RESISTANCE; INFECTION; RISK; LOCI;

D O I：

10.1038/s42003-021-02549-5

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 10(-10), allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 x 10(-9), AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 x 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. Chaolong Wang and colleagues report a large genome-wide association study for COVID-19 severity in Chinese individuals. By meta-analysis with European data, they identify 3 loci associated with severe disease that suggest key roles for the adaptive immune system and the ABO blood group system in development of severe COVID-19.

引用

页数：10

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