整个基因组测序揭示了COVID-19的潜在关键宿主因素
Athanasios Kousathanas1, Erola Pairo-Castineira2,3, Konrad Rawlik2
1Genomics England, London, UK.
Nature
|March 7, 2022
概括
遗传变异显著增加了严重的COVID-19的风险. 研究人员发现了23种基因变异,包括免疫和血型基因的新关联,为严重的呼吸系统疾病提供了潜在的治疗点.
科学领域:
- 遗传学
- 免疫学
- 危急护理医学
背景情况:
- 严重的COVID-19是由免疫介导的炎症性肺损伤引起的.
- 宿主基因变异会影响SARS-CoV-2感染的严重程度.
- 在GenOMICC研究中,重症患者的基因组与人口对照进行了比较.
研究的目的:
- 识别使个人易患危急COVID-19的遗传变异.
- 发现潜在的疾病机制和潜在的治疗点.
主要方法:
- 全基因组测序 7,491 个重病患者和 48,400 个对照人群.
- 转录组范围的关联和同地化分析.
- 孟德尔的随机化研究.
主要成果:
- 发现并复制了与危急COVID-19相关的23种独立变异.
- 发现了16种新的关联,包括干扰素信号传递基因 (IL10RB,PLSCR1),白细胞分化 (BCL11A) 和分泌物状态 (FUT2).
- 证据表明基因表达变化 (例如ATP11A,MUC1) 并确定潜在的药物标 (SELE,ICAM5,CD209,F8).
结论:
- 遗传因素在严重的COVID-19病变中起着至关重要的作用.
- 两种主要机制导致危及生命的疾病:病毒控制受损或炎症/凝血加剧.
- 将危急病例与对照病例进行比较是有效的治疗点.
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