Cheng Zhongshan, Cai Yi, Zhang Ke, Zhang Jingxuan, Gui Hongsheng, Luo Yu-Si, Zhou Jie, DeVeale Brian
Center for Applied Bioinformatics, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA.
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518000, China.
iScience. 2023 Aug 7;26(9):107555. doi: 10.1016/j.isci.2023.107555. eCollection 2023 Sep 15.
To identify ancestry-linked genetic risk variants associated with COVID-19 hospitalization, we performed an integrative analysis of two genome-wide association studies and resolved four single nucleotide polymorphisms more frequent in COVID-19-hospitalized patients with non-European ancestry. Among them, the COVID-19 risk SNP rs16831827 shows the largest difference in minor allele frequency (MAF) between populations with African and European ancestry and also shows higher MAF in hospitalized COVID-19 patients among cohorts of mixed ancestry (odds ratio [OR] = 1.20, 95% CI: 1.10-1.30) and entirely African ancestry (OR = 1.30, 95% CI: 1.02-1.67). rs16831827 is an expression quantitative trait locus of . expression is induced during ciliogenesis and most abundant in ciliated tissues including lungs. Single-cell RNA sequencing analyses revealed that is highly expressed in multiple ciliated cell types. As rs16831827∗T is associated with reduced expression, it may increase the risk of severe COVID-19 by reducing expression.
为了识别与新冠病毒住院治疗相关的祖先关联遗传风险变异，我们对两项全基因组关联研究进行了综合分析，并确定了4个单核苷酸多态性，这些多态性在非欧洲血统的新冠病毒住院患者中更为常见。其中，新冠病毒风险单核苷酸多态性rs16831827在非洲和欧洲血统人群之间的次要等位基因频率（MAF）差异最大，并且在混合血统队列（优势比[OR]=1.20，95%置信区间：1.10-1.30）和完全非洲血统队列（OR=1.30，95%置信区间：1.02-1.67）的新冠病毒住院患者中也显示出更高的MAF。rs16831827是……的表达数量性状位点。……的表达在纤毛发生过程中被诱导，并且在包括肺在内的纤毛组织中最为丰富。单细胞RNA测序分析显示，……在多种纤毛细胞类型中高度表达。由于rs16831827∗T与……表达降低相关，它可能通过降低……表达增加严重新冠病毒感染的风险。
