Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population.
Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population.
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DOI：
10.1371/journal.pone.0276700
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
COVID-19是由严重急性呼吸综合征-冠状病毒-2 （SARS-CoV-2）引起的。COVID-19的严重程度变化很大，与已知（如年龄、肥胖、免疫缺陷）和未知的风险因素有关。广泛的临床症状包括大量无症状的COVID-19患者，这就提出了一个关于遗传易感性的关键问题，例如，免疫的个体差异是否在患者症状中起作用，以及人类白细胞抗原（HLA）在其中起多大作用。为了揭示人群对COVID-19严重程度易感性的遗传决定因素，并进一步探索潜在的免疫相关因素，我们对284例确诊的COVID-19患者（病例）和95名健康个体（对照组）进行了全基因组关联研究。我们分别比较了欧洲（EUR）血统和非裔美国（AFR）血统的病例和对照。我们在5q32和11p12染色体上发现了两个位点，它们达到了暗示关联的显著性阈值（p<1 × 10-5多性状检验调整阈值），并且与欧洲血统的COVID-19易感性相关(指数rs17448496：优势比[OR] = 0.173； 95%可信区间[CI]， G等位基因为0.08-0.36;p = 5.15× 10-5；指数rs768632395: OR = 0.166；p = 4.25×10−6)，这两个基因分别与位于5q32的PPP2R2B和位于11p12的LRRC4C相关。为了探索HLA与COVID-19严重程度之间的联系，我们采用精细映射分析来剖析HLA与轻、重度病例的关系。利用硅结合预测来绘制风险/保护性HLA与病毒结构蛋白的结合图谱，我们发现在两个祖先中病毒肽的差异表现。最后，将该队列中确定的HLA外推到全球人群中，发现了显著的相关性。该研究揭示了遗传背景下不同祖先对COVID-19的易感性可能存在的差异，可能为该病的发病机制和临床治疗提供新的见解。
COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. The widespread clinical symptoms encompass a large group of asymptomatic COVID-19 patients, raising a crucial question regarding genetic susceptibility, e.g., whether individual differences in immunity play a role in patient symptomatology and how much human leukocyte antigen (HLA) contributes to this. To reveal genetic determinants of susceptibility to COVID-19 severity in the population and further explore potential immune-related factors, we performed a genome-wide association study on 284 confirmed COVID-19 patients (cases) and 95 healthy individuals (controls). We compared cases and controls of European (EUR) ancestry and African American (AFR) ancestry separately. We identified two loci on chromosomes 5q32 and 11p12, which reach the significance threshold of suggestive association (p<1x10-5 threshold adjusted for multiple trait testing) and are associated with the COVID-19 susceptibility in the European ancestry (index rs17448496: odds ratio[OR] = 0.173; 95% confidence interval[CI], 0.08–0.36 for G allele; p = 5.15× 10−5 and index rs768632395: OR = 0.166; 95% CI, 0.07–0.35 for A allele; p = 4.25×10−6, respectively), which were associated with two genes, PPP2R2B at 5q32, and LRRC4C at 11p12, respectively. To explore the linkage between HLA and COVID-19 severity, we applied fine-mapping analysis to dissect the HLA association with mild and severe cases. Using In-silico binding predictions to map the binding of risk/protective HLA to the viral structural proteins, we found the differential presentation of viral peptides in both ancestries. Lastly, extrapolation of the identified HLA from the cohort to the worldwide population revealed notable correlations. The study uncovers possible differences in susceptibility to COVID-19 in different ancestral origins in the genetic background, which may provide new insights into the pathogenesis and clinical treatment of the disease.
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DOI：
10.15585/mmwr.mm6915e3
发表时间：
2020-04-17
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Garg S;Kim L;Whitaker M;O'Halloran A;Cummings C;Holstein R;Prill M;Chai SJ;Kirley PD;Alden NB;Kawasaki B;Yousey-Hindes K;Niccolai L;Anderson EJ;Openo KP;Weigel A;Monroe ML;Ryan P;Henderson J;Kim S;Como-Sabetti K;Lynfield R;Sosin D;Torres S;Muse A;Bennett NM;Billing L;Sutton M;West N;Schaffner W;Talbot HK;Aquino C;George A;Budd A;Brammer L;Langley G;Hall AJ;Fry A
通讯作者：
Fry A
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
影响因子：
12.7
作者：
Naemi，Fatmah M. A.;Al-adwani，Shurooq;Al-nazawi，Ashwaq
通讯作者：
Al-nazawi，Ashwaq
人白细胞抗原复合物以及其他免疫遗传和临床因素会影响对SARS-COV-2感染和疾病病程严重程度的敏感性或保护。撒丁岛的经历。
影响因子：
7.3
作者：
Littera R;Campagna M;Deidda S;Angioni G;Cipri S;Melis M;Firinu D;Santus S;Lai A;Porcella R;Lai S;Rassu S;Scioscia R;Meloni F;Schirru D;Cordeddu W;Kowalik MA;Serra M;Ragatzu P;Carta MG;Del Giacco S;Restivo A;Deidda S;Orrù S;Palimodde A;Perra R;Orrù G;Conti M;Balestrieri C;Serra G;Onali S;Marongiu F;Perra A;Chessa L
通讯作者：
Chessa L