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.

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Background Tinnitus is an auditory phantom sensation in the absence of an acoustic stimulus, which affects nearly 15% of the population. Excessive noise exposure is one of the main causes of tinnitus. To now, the knowledge of the genetic determinants of susceptibility to tinnitus remains limited. Results We performed a two-stage genome-wide association study (GWAS) and identified that two single nucleotide polymorphisms (SNPs), rs2846071 located in the intergenic region at 11q13.5 (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.96–3.40, combined P = 4.89 × 10− 6) and rs4149577 located in the intron of TNFRSF1A gene at 12p13.31 (OR = 2.05, 95% CI = 1.89–2.51, combined P = 6.88 × 10− 6), are significantly associated with the susceptibility to noise-induced tinnitus. Furthermore, the expression quantitative trait loci (eQTL) analyses revealed that rs2846071 is significantly correlated with the expression of WNT11 gene, and rs4149577 with the expression of TNFRSF1A gene in multiple brain tissues (all P < 0.05). The newly identified candidate gene WNT11 is involved in Wnt pathway, and TNFRSF1A in the tumor necrosis factor pathway, respectively. Pathway enrichment analyses also showed that these two pathways are closely relevant to tinnitus. Conclusions Our findings highlight two novel loci at 11q13.5 and 12p13.31 conferring susceptibility to noise-induced tinnitus. and suggest that the WNT11 and TNFRSF1A genes might be the candidate causal targets of 11q13.5 and 12p13.31 loci, respectively.