Abstract
Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10 -15 , OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10 -3 , OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10 -16 , OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.
【초록키워드】 COVID-19, coronavirus disease, Coronavirus disease 2019, IL-6, Variation, Genetic, variant, in vitro, serum, Cohort, male, Patient, Genotype, Genome-wide association study, Control, Genetic variant, threshold, expression, Critical, association, Analysis, Asymptomatic COVID-19, genetic factors, Formal, Factor, healthy control, Chinese, high mortality, critical condition, healthy controls, G allele, luciferase, IL-6 expression, genome-wide significance, PROTECT, responsible, identify, performed, significantly, involved, recruited, reported, changes in, replicated, genome-wide significant, luciferase expression, patients with asymptomatic, patients with COVID-19, surpassed, with COVID-19, 【제목키워드】 expression, Critical, Protective, patients with COVID-19,