Comparative genetic analysis of 2019-nCoV receptor ACE2 in different populations
nature.com
nature.com
The paper implicates the ACE2 gene that encodes a protein that acts as a receptor for covid-19 (and SARS) - based on studies showing the correlation of SARS infection with ACE2 expression. The paper investigates which mutations (variants) in human genomes could lead to lower expression of ACE2 (lower activity levels of the gene, meaning less receptors for covid-19).
However, in China, there weren't that many: "These data suggested that there was a lack of natural resistant mutations for coronavirus S-protein binding in populations."
32 candidate variants are identified, so if you have done whole genome sequencing of your DNA, you can get some very rough estimate of your suspectability to acquiring covid-19 - if you have a mutation or two there. Naturally sub-saharan Africans have higher genomic diversity, so there's probably more protective mutations in their population.
The only thing I've found so far is this:
https://bmcpulmmed.biomedcentral.com/articles/10.1186/1471-2...
The CF community seems to be assuming this will be very bad for anyone with CF, but the reality is CF exists because it's like Sickle Cell: it's protective against some infections.
CF community links:
https://www.cfireland.ie/about-cf/latest-news/cfi-update-cor...
https://www.reddit.com/r/CysticFibrosis/comments/fb4cz7/the_...
First-hand experience suggests it protects against Winter Vomiting, a deadly flu that went around years ago.
For example, I found: https://www.ncbi.nlm.nih.gov/pubmed/26527495 which is a single author hypothesis.
I'm aware that it's just a hypothesis that it protects against cholera and tuberculosis. My confidence that it protects against some things is based primarily on first-hand experience.
I and my oldest son both have a form of CF. About 18 years ago, not long after we were diagnosed, my other son came down with Winter Vomiting. It was a particularly deadly flu. He spent 8 days laying in bed, mostly not eating.
I told him at some point that if he became too dehydrated, I would take him to the ER for an IV. He had an IV once before and didn't want another one. So once a day, he would eat a few crackers or some ramen and drink about 32 ounces of water and promptly projectile vomit everything back up.
He was utterly miserable for more than a week.
Meanwhile, I and my oldest son felt sort of blah for maybe a day and a half. We routinely felt blah. That's entirely normal given our genetic disorder.
We would have never known we had been exposed to Winter Vomiting had my other son not been so horrendously sick with it.
So that's the primary basis of my opinion that it's like Sickle Cell and is more common in some populations due to being protective against some things that, historically, those populations were exposed to a great deal.
I'm not trying to convince you of anything. I'm only explaining why I think it makes sense. You will need to decide for yourself what makes sense to you and what kind of research is adequately compelling to convince you of a thing.
Please don't turn this into some weird thing where you feel some need to follow me around from conversation to conversation and harangue me and prove me wrong and so forth. Far too many internet strangers have done things like that to me. I was commenting here in hopes of more accurately assessing risks for me and my sons, not in hopes of convincing the world to see things X way.
You aren't required to agree with me. By the same token, I'm not required to agree with you.
Good luck in finding answers that adequately satisfy you. But I can't really help you with that.
Does this implies somehow that people with high blood pressure are more at risk of covid-19 infection?
* diversity is quite different from evolution
Nothing is an excuse for abandoning proper science. On top of that you editorialize a correspondence that doesn't even strongly support the claim the title suggests. From the correspondence itself:
> However, the genetic basis of ACE2 expression and function in different populations is still largely unknown.
> Recent reports of the ACE2 expression analysis in lung tissues from Asian and Caucasian populations are still controversial. The single-cell RNA-seq analysis reported that the Asian donor had much higher ACE2 expression cell ratio than white and African-American donors6. In contrast, the ACE2 expression analysis using the RNA-seq and microarray datasets from control lung tissues indicated there were no significant differences between Asian and Caucasian, or male and female
> semi-informed guess
That is the last thing you should be doing in a life-threatening situation.
It's a big enough commitment that he no doubt doesn't want to jump the gun and do so with zero justification. But erring on the side of caution is absolutely the correct thing to do if you are responsible for two people at potentially very high risk (of death) due to the current situation concerning covid19.
If the situation is as serious as you purport it to be then perhaps they should actually dig into the science instead of relying on the interpretation of some random HN poster.
Where peer review is critical is the first pass filter. I can't read all the literature, so I need some editorial filter in place. I may reject the findings in a peer-reviewed paper (or even worse, find the results uninteresting), but helping to decide what to read is critical. For those in the business, all papers get integrated into our mental models for how things work, and data that is a bit odd simply means we need to put more focus there.
That said, an issue is present when a field systematically produces bad papers - how do you navigate that?!
It depends on what your goal is. If it is for personal edification that you don't need to justify to anyone else:
1. Collect tidbits with a high confidence level.
2. Check to see if the way the thing was tested makes sense to you.
3. Check to see if it generally makes sense and fits with what little you do know with a fairly high confidence level.
Our findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations
...
The East Asian populations have much higher AFs in the eQTL variants associated with higher ACE2 expression in tissues (Fig. 1c), which may suggest different susceptibility or response to 2019-nCoV/SARS-CoV-2 from different populations under the similar conditions.
On a larger note, I am very surprised that death rates are calculated so naively by many and potential uncertainties are not accounted for. Like: high number of undetected cases, because of very mild cases. Skewed population factors like smoking, and genetics.
(1) https://fortune.com/2020/02/19/coronavirus-china-smoking-rat...
yes the recovery data seems delayed, there are 3000+ koreans affected and only 30 recovered. While half of chinese have recovered.
Also, numbers from Iran can definitely not be trusted
On the cruise ship, about a third of the cases are asymptomic [1].
[1] https://www.medrxiv.org/content/10.1101/2020.02.20.20025866v...
This is bullshit. There's no other word for it.
The article claims that:
> Previous studies demonstrated the positive correlation of ACE2 expression and the infection of SARS-CoV in vitro
But them goes on to qualify its point with:
> However, the genetic basis of ACE2 expression and function in different populations is still largely unknown.
> Recent reports of the ACE2 expression analysis in lung tissues from Asian and Caucasian populations are still controversial. The single-cell RNA-seq analysis reported that the Asian donor had much higher ACE2 expression cell ratio than white and African-American donors6. In contrast, the ACE2 expression analysis using the RNA-seq and microarray datasets from control lung tissues indicated there were no significant differences between Asian and Caucasian, or male and female
It also goes into detail about genetic variants/eQLTs that affect ACE2 production and their prevalence in different populations . This is the actual meat of the article and is only loosely related to the title. It claims that certain eQTLs that cause lower expression of ACE2 are more common in certain populations than others. However if you look at the actual numbers the most common one happens at an allele frequency of .2124 in African populations. If you look at the pie charts in figure 1c you will find the distribution in orange of one of what seems to be the most common variant(assosciated with high expression of ACE2), which makes up a majority in all populations examined. The actual effects of each eQTL is found in supplementaty table 3:
o-https://static-content.springer.com/esm/art%3A10.1038%2Fs414...
Mods: Please change the submission title to the actual article title.
The real crux of this article is that they pulled out genetic variants associated with expression levels of ACE2 (from gtex, which should be solid enough). These variants are more prevalent in east asian populations.
There's a paper they reference too saying that there's a subset of cells that express ACE2 in the lungs, which doesn't really support expression levels being changed, but could point to the cell system that could be used to investigate this.
Nothing really solid yet about dose dependence of ACE2 on SARS-CoV-2 susceptibility. Interesting though!
https://www.wired.com/story/covid-19-is-traveling-along-the-...
> The Han Chinese are truly a large population. They have been mixing freely for thousands of years. In contrast, there are few if any Indian groups that are demographically very large, and the degree of genetic differentiation among Indian jati groups living side by side in the same village is typically two to three times higher than the genetic differentiation between northern and southern Europeans. The truth is that India is composed of a large number of small populations.
--
Now will come my unscientific and probably not well enough put together note but hopefully it make some sense: if there is something genetical which makes this disease a bigger problem in the Han Chinese population thne that is very likely to be everywhere unless it's really a very new mutation. On the other hand, it's possible the mutation won't be found in every population in India.
Looking at SARS statistics https://www.who.int/csr/sars/country/table2004_04_21/en/ look at the high number of cases in Singapore where 75% is Han Chinese.