PDF(Pubmed)
Abstract：
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women.
摘要：
2019年冠状病毒病（COVID-19）大流行，由严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）引起，已导致全球超过640万人死亡。高血压和严重COVID-19之间普遍存在的共病表明共同的遗传因素可能会影响两种疾病的预后。由于高血压和严重的COVID-19都表现出性别偏见的患病率，两种疾病之间的共同遗传因素可能显示出性别偏见的差异关联。通过评估来自英国生物银行与欧洲血统的两项性别分层的严重COVID-19全基因组关联研究中，来自超过100万欧洲个体的172个候选高血压单核苷酸多态性（SNP）的COVID-19关联信号，我们揭示了SPEG的一个功能性顺式表达数量性状基因座（rs12474050），显示出与女性严重COVID-19的性别偏倚性关联。风险等位基因rs12474050*T与较高的血压相关。在我们的研究中,我们发现它与肌肉-骨骼中SPEG表达较低有关，但在大脑小脑和小脑半球中的表达较高。此外,检测到rs12474050*T与心脏左心室和心耳中较低SPEG表达之间的关联的名义意义；在这些组织中，女性的SPEG表达名义上显著高于男性。进一步分析显示，SPEG主要在心脏心肌细胞中表达，并在SARS-CoV-2感染后上调，与正常的女性和男性个体相比，仅在女性中观察到SPEG的上调，而在男性COVID-19患者中没有观察到，提示上调SPEG是针对COVID-19诱导的心脏损伤的女性特异性保护机制。一起来看,我们的分析表明，SPEG参与女性高血压和严重COVID-19，这为女性严重COVID-19的性别偏倚效应提供了新的见解。
