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Abstract：
There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.
We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.
We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5).
We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).
We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.
We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5).
We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).
摘要：
感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的患者的疾病行为存在相当大的差异，导致2019年冠状病毒病的病毒（Covid-19）。全基因组关联分析可能有助于鉴定参与新冠肺炎发育的潜在遗传因素。
我们在欧洲SARS-CoV-2大流行的意大利和西班牙的七家医院进行了一项全基因组关联研究，涉及1980例Covid-19和严重疾病（定义为呼吸衰竭）患者。在质量控制和排除人口异常值之后，最终分析包括来自意大利的835名患者和1255名对照参与者以及来自西班牙的775名患者和950名对照参与者。总的来说,我们分析了8,582,968个单核苷酸多态性,并对两个病例对照小组进行了荟萃分析.
我们检测到与3p21.31位点的rs11385942和9q34.2位点的rs657152的交叉复制关联，在两个病例对照面板的荟萃分析中，这在全基因组水平（P<5×10-8）上是显着的（优势比，1.77；95%置信区间[CI]，1.48至2.11；P=1.15×10-10；赔率比，1.32；95%CI，1.20至1.47；分别为P=4.95×10-8）。在基因座3p21.31,关联信号跨越基因SLC6A20、LZTFL1、CCR9、FYCO1、CXCR6和XCR1。9q34.2位点的关联信号与ABO血型位点一致；在这个队列中，血型特异性分析显示，血型A的风险高于其他血型(比值比，1.45；95％CI，1.20至1.75；P=1.48×10-4），与其他血型相比，O血型具有保护作用（比值比，0.65；95%CI，0.53至0.79；P=1.06×10-5）。
我们确定了3p21.31基因簇是新冠肺炎呼吸衰竭患者的遗传易感位点，并证实了ABO血型系统的潜在参与。（由SteinErikHagen和其他人资助。).
我们在欧洲SARS-CoV-2大流行的意大利和西班牙的七家医院进行了一项全基因组关联研究，涉及1980例Covid-19和严重疾病（定义为呼吸衰竭）患者。在质量控制和排除人口异常值之后，最终分析包括来自意大利的835名患者和1255名对照参与者以及来自西班牙的775名患者和950名对照参与者。总的来说,我们分析了8,582,968个单核苷酸多态性,并对两个病例对照小组进行了荟萃分析.
我们检测到与3p21.31位点的rs11385942和9q34.2位点的rs657152的交叉复制关联，在两个病例对照面板的荟萃分析中，这在全基因组水平（P<5×10-8）上是显着的（优势比，1.77；95%置信区间[CI]，1.48至2.11；P=1.15×10-10；赔率比，1.32；95%CI，1.20至1.47；分别为P=4.95×10-8）。在基因座3p21.31,关联信号跨越基因SLC6A20、LZTFL1、CCR9、FYCO1、CXCR6和XCR1。9q34.2位点的关联信号与ABO血型位点一致；在这个队列中，血型特异性分析显示，血型A的风险高于其他血型(比值比，1.45；95％CI，1.20至1.75；P=1.48×10-4），与其他血型相比，O血型具有保护作用（比值比，0.65；95%CI，0.53至0.79；P=1.06×10-5）。
我们确定了3p21.31基因簇是新冠肺炎呼吸衰竭患者的遗传易感位点，并证实了ABO血型系统的潜在参与。（由SteinErikHagen和其他人资助。).
