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.
【저자키워드】 viral infection, Genome-wide association studies, 【초록키워드】 COVID-19, Meta-analysis, Adaptive immunity, Hospitalized, adaptive, severe COVID-19, Clinical symptoms, Immunity, allele frequency, Infection, COVID-19 severity, Symptoms, Patient, Genome-wide association study, Control, Mild, Genetic variant, Blood Group, ABO, Odds ratio, severe disease, followed by, blood group system, Chinese, COVID-19 Host Genetics Initiative, clinical development, Severe case, insertion, loci, adaptive immune system, frameshift, allele frequencies, genome-wide association, FOXP4, FOXP4-AS1, initiative, intronic variant, MEF2B, rs8176719, European, controls, highlight, tested, identify, caused, sequenced, contributing to, individuals, genotyped, 【제목키워드】 Genome-wide association study,