Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38–0.63 for T allele; P = 1.38 × 10−8; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele; P = 4.04 × 10−8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.
Highlights
A novel coronavirus disease 2019 (COVID-19)caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly throughout the world[1], and has already affected over 110 million individuals worldwide, causing more than 2.5 million deaths (WHO, 2021, https://covid19.who.int; up to 8 March, 2021)
We performed genome-wide association tests adjusting for age, gender, comorbidities, and the top 10 or 20 principal components from principal component analysis (PCA)
When adding the naïve controls (n = 954) in the association test, we found that the blood group A was significantly associated with higher risk of the severity of COVID-19 (OR = 1.22, P = 3.2 × 10−4; Supplementary Table S12), and the blood group O was significantly associated with lower risk of severity of COVID19 (OR = 0.83, P = 1.5 × 10−3; Supplementary Table S12)
Summary
A novel coronavirus disease 2019 (COVID-19)caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly throughout the world[1], and has already affected over 110 million individuals worldwide, causing more than 2.5 million deaths (WHO, 2021, https://covid19.who.int; up to 8 March, 2021). Reports have shown that elder age, male sex, and comorbid conditions (including hypertension, diabetes, and coronary artery diseases) are risk factors for the development of COVID-197–11, but the extent to which genetic factors might influence susceptibility to the SARS-CoV-2 infection or disease severity remains largely unknown. High-throughput sequencing studies have identified rare loss-of-function variants in toll-like receptor 7 (TLR7) in Dutch severe COVID-19 patients[13], and several genes involved in type I interferon (IFN) pathway in severe COVID-19 patients (most of whom are of European ancestry)[14]. Two genome-wide association studies (GWASs) in populations of European ancestry identified six loci to be significantly associated with COVID-19 severity[15,17], including 3p21.31 (index single nucleotide polymorphism [SNP]: rs11385942), 9q34.2 (rs657152), 12q24.13 (rs10735079), 19p13.2 (rs74956615), 19p13.3 (rs2109069), and 21q22.1 (rs2236757). To identify novel loci for COVID-19 severity, we performed a GWAS of COVID-19 severity among the Chinese population
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