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Trans-ethnic genome-wide association study of severe COVID-19 #MMPMID34465887
Wu P; Ding L; Li X; Liu S; Cheng F; He Q; Xiao M; Wu P; Hou H; Jiang M; Long P; Wang H; Liu L; Qu M; Shi X; Jiang Q; Mo T; Ding W; Fu Y; Han S; Huo X; Zeng Y; Zhou Y; Zhang Q; Ke J; Xu X; Ni W; Shao Z; Wang J; Liu P; Li Z; Jin Y; Zheng F; Wang F; Liu L; Li W; Liu K; Peng R; Xu X; Lin Y; Gao H; Shi L; Geng Z; Mu X; Yan Y; Wang K; Wu D; Hao X; Cheng S; Qiu G; Guo H; Li K; Chen G; Sun Z; Lin X; Jin X; Wang F; Sun C; Wang C
Commun Biol 2021[Aug]; 4 (1): 1034 PMID34465887show ga
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.