2022年6月14日

新的研究发现了1000多个与严重COVID-19有关的基因

研究ers from the University of 谢菲尔德 and Stanford University in the US have discovered there are specific genetic signals in people who develop severe coronavirus infection.

病毒爆炸的未来设计

  • University of 谢菲尔德 research collaboration with Stanford University reveals why some healthy adults with the COVID-19 infection become seriously ill, 而其他人则很少有症状
  • 众所周知,年龄, body mass index and pre-existing health problems account for some of the disparities, 但基因也发挥了重要作用
  • The new research suggests there are specific genetic signals in people who develop a severe coronavirus infection
  • 国际研究团队已经确定超过1,000 genes linked to the development of severe COVID-19 and which particularly affect the function of a certain type of white blood cell known as Natural Killer, 或NK细胞. 

研究ers from the University of 谢菲尔德 and Stanford University in the US have discovered there are specific genetic signals in people who develop a severe coronavirus infection.  

众所周知,年龄, body mass index and pre-existing health problems account for some of the disparities, 但基因也发挥了重要作用. This pioneering research aimed to address why some people with COVID-19 become seriously ill or die, 而其他人则很少, 如果有任何, 症状.

使用机器学习, researchers from the University of 谢菲尔德 and Stanford Medicine have identified more than 1,000 genes linked to the development of severe COVID-19 cases that required breathing support, 或是致命的. The team was also able to identify specific types of cells in which those genes act up. It’s one of the first studies to link coronavirus-associated genes to specific biological functions.

jonathan Cooper-Knock博士, NIHR Clinical Lecturer in the 神经科学系 at the University of 谢菲尔德 and co-author of the study, 说:

“During the research we discovered the genetic architecture underlying coronavirus infection, 发现这1,000 genes account for three quarters of the genetic drivers for severe COVID-19. This is significant in understanding why some people have had more severe 症状 of 新型冠状病毒肺炎 than others.”

这项研究, 该研究发表在今天(2022年6月14日)的《188bet金宝搏官网登录》杂志上, was led by Senior Author Professor Michael P Snyder from the University of Stanford in collaboration with genetics instructor Dr Sai Zhang and neuroscientist Cooper-Knock博士, 谁是斯坦福大学的访问学者.

研究过程

The research team used several large data sets to unpack the genetics behind severe COVID-19. The first data set contained genetic information from healthy human lung tissue. The data helped identify gene expression in 19 different types of lung cells, including epithelial cells that line the respiratory tract and are the first defence against infection.

其他数据来自COVID-19宿主遗传学计划, 这是最大规模的冠状病毒危重患者基因研究之一. 研究人员在数据中寻找基因线索——DNA突变, called single nucleotide polymorphisms — that might indicate if someone is at a higher risk for severe COVID-19. They tracked whether some mutations occurred more or less often in COVID-19 patients with severe disease.

不断出现的突变, 或者明显缺席, in the patients who developed severe COVID-19 suggested those variations might be behind the infection’s severity.

但是基因突变本身很难解释. To better understand their findings the team used other data describing which regions of the genome are important for different cell types within lung tissue. By overlapping the mutations onto the cell-specific genomes the researchers could pinpoint which genes were dysfunctioning and within which cell-types.
 
风险基因

The researchers also wanted to know which types of cells harboured faulty gene expression. 通过机器学习工具, they determined that severe COVID-19 is largely associated with a weakened response from two well-known immune cells — natural killer (NK) cells and T cells. NK cells and a subtype called ‘CD56 bright’ are considered the most important.

Cooper-Knock博士补充道: “NK细胞, which humans are born with and are the body’s first line of defence against infection, 以摧毁病毒和癌细胞的能力而闻名. NK cells also help produce a range of immune system proteins called cytokines. 其中一种细胞因子,干扰素,是免疫细胞的关键激活因子. 与干扰素协同作用, NK cells mount an immediate and coordinated defence against viral infections.

“朝鲜细胞就像指挥战争的将军. 它们动员其他免疫细胞,告诉它们去哪里,做什么. 188bet金宝搏官网登录发现,在冠状病毒严重感染的人群中, NK细胞中关键基因表达减少, 所以免疫反应不那么强烈. 细胞没有做它应该做的事.”

Professor Snyder likened COVID-19 risk genes to harmful variants of the BRCA genes that predispose some people to breast and ovarian cancer.

斯奈德教授说: “Our findings lay the foundation for a genetic test that can predict who is born with an increased risk for severe COVID-19.

“想象一下,有1000个DNA变化与严重的COVID-19有关. 如果有585个这样的变化, 这可能会让你很容易受到影响, 你要采取所有必要的预防措施.”

Cooper-Knock博士 also noted drugs that kickstart sluggish NK cells are already proposed to treat some types of cancer. “The drugs bind to receptors on the NK cells and trigger them to have a more robust response,他说. NK细胞输注治疗重症COVID-19的试验正在进行中.”

额外的信息 
研究ers from the University of 谢菲尔德; the Jackson Laboratory for Genomic Medicine; the University of Siena; Azienda Ospedaliero-Universitaria Senese; University Medical Center Utrecht; University of Edinburgh; University of Edinburgh, Western General Hospital; Royal Infirmary of Edinburgh; and the VA Palo Alto Health Care System also contributed to the work.