1. Trans-ethnic genome-wide association study of severe COVID-19.
- Author
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Wu, Peng, Ding, Lin, Li, Xiaodong, Liu, Siyang, Cheng, Fanjun, He, Qing, Xiao, Mingzhong, Wu, Ping, Hou, Hongyan, Jiang, Minghui, Long, Pinpin, Wang, Hao, Liu, Linlin, Qu, Minghan, Shi, Xian, Jiang, Qin, Mo, Tingting, Ding, Wencheng, Fu, Yu, and Han, Shi
- Subjects
COVID-19 pandemic ,GENETIC variation ,GENOTYPES ,ABO blood group system ,GENOME-wide association studies - 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. 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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