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Comparative genetic analysis of 2019-nCoV receptor ACE2 in different populations
- jamesblonde 7y agoI posted/read this article, because I (1) have worked a bit with genomic data and I can read their papers and (2) I have full genome sequenced my family. 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.
- mquander 7y agoSorry for the small derail, but can you comment on your decision to sequence your family? I considered doing this recently but it wasn't clear to me that I would obtain much actionable information, so I declined to expend the effort. (After all, it will only get cheaper and easier.)
- jamesblonde 7y agoI will check to see if we have many of the ACE variants defined in the paper to get an idea of where we stand. Although it is still just probabilities, it might mean the difference between moving to the summer house for 6 months with them or staying in the city. I could work remote, so that's a possibility.
- DoreenMichele 7y agoI'm just a lay person. Would you be able to say anything (or point me to anything) about the relationship between ACE2 and the CFTR? The only thing I've found so far is this: https://bmcpulmmed.biomedcentral.com/articles/10.1186/1471-2466-12-41 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-coronavirus-disease-cov-19 https://www.cfireland.ie/about-cf/latest-news/cfi-update-cor... https://www.reddit.com/r/CysticFibrosis/comments/fb4cz7/the_potential_danger_of_covid19_coronavirus_to/ https://www.reddit.com/r/CysticFibrosis/comments/fb4cz7/the_...
- jamesblonde 7y agoTwo of my boys have CF, so i have skin in this game. They are young, which is positive. The economist are saying that it is expected that 25-70% of people globally will get infected, so i am worried. But I haven't found out anything yet.
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- ekelsen 7y agoWhat infections does having one copy of the CF gene protect against? The wikipedia page suggests this is an unproven hypothesis.
- DoreenMichele 7y agoResearch suggests cholera and tuberculosis. First-hand experience suggests it protects against Winter Vomiting, a deadly flu that went around years ago.
- ekelsen 7y agoI can't find any studies that confirm cholera or tuberculosis. Do you have any citations? For example, I found: https://www.ncbi.nlm.nih.gov/pubmed/26527495 https://www.ncbi.nlm.nih.gov/pubmed/26527495 which is a single author hypothesis.
- JPLeRouzic 7y agoThanks, Does this implies somehow that people with high blood pressure are more at risk of covid-19 infection?
- jamesblonde 7y agoNo, it says nothing about blood pressure. It is about which genetic variants you have that determine the level of angiotensin-converting enzyme-2 in your body. If you have more of it, you probably have a higher chance of acquiring corona-viruses.
- fouc 7y agoHigher genomic diversity is just another way of saying there's more ethnic groups in Africa, right? So it's not particularly a racial thing.
- afiori 7y agoif I remember correctly from a genetic perspective the group of "not African ethnicities" is more uniform than the group of "African ethnicities"
- xiphias2 7y agoIt's a historical thing: humans were evolving for much longer time in Africa than in other continents.
- username90 7y agoAll humans have evolved for the same amount of time. It is just that a smaller part of the population decided to emigrate than to stay a long time ago.
- bonzini 7y agoMigration causes a genetic bottleneck that (sort of) resets the counter.
- afiori 7y agoyes, but for much longer in Africa than outside of Africa. If you assume that "diversity" increases mostly steadily over time* then there is much more diversity in Africa than in the rest of the world. * diversity is quite different from evolution
- baxtr 7y agoHighly interesting. Add to that the fact that 50% of all men in China smoke and you might end up with a higher mortality rate than elsewhere (1). 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-rate-men/ https://fortune.com/2020/02/19/coronavirus-china-smoking-rat...
- Geee 7y agoIt's still too early to tell, and it's just not possible to make accurate calculations if the data itself is missing. It's known that there aren't a lot of mild cases. Also, the mortality doesn't seem to be lower elsewhere. For example, in Iran there is 43 deaths and 123 recovered, and in Italy 29 deaths and 50 recovered.
- mkagenius 7y ago> Italy 29 deaths and 50 recovered. yes the recovery data seems delayed, there are 3000+ koreans affected and only 30 recovered. While half of chinese have recovered.
- lbeltrame 7y agoIt also depends on the definition of "recovered". Our first recovered patient was called such only after almost a week of repeated tests. Which means that the data will lag considerably compared to deaths and new infections.
- baxtr 7y agoHow do you know they aren’t a lot of mild cases that go undetected? From what I’ve read 80%+ are mild, only 10-15% severe, at least in Europe. Most clusters can’t be backtracked to patient zero anymore Also, numbers from Iran can definitely not be trusted
- yodsanklai 7y ago
- legulere 7y agoThis is not even a peer reviewed paper but just a comment. The title is completely editorialized to something the article doesn’t state. https://www.nature.com/nature/for-authors/other-subs https://www.nature.com/nature/for-authors/other-subs
- jamesblonde 7y agoIf we want timely research on covid-19, we can't wait for peer-review. The title reflects this statement in the paper: "the differences in AFs of ACE2 coding variants among different populations suggested that the diverse genetic basis might affect ACE2 functions among populations....ACE2 gene encodes the angiotensin-converting enzyme-2, which has been proved to be the receptor for both the SARS-coronavirus (SARS-CoV) and the human respiratory coronavirus NL63.
- knolax 7y ago> If we want timely research on covid-19, we can't wait for peer-review. 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
- DoreenMichele 7y agoPeople with life-threatening situations sometimes are less interested in proper science and more interested in timely information upon which they can base some kind of semi-informed guess as to just how much extreme paranoia seems justified.
- finneganscat 7y agoAny idea if taking an ACE inhibitor blood pressure med would change the likelihood of contracting the virus?
- econcon 7y agoIt seems strange to me that Italy and Iran are affected but India is not. I don't think India is better equipped, I wonder if reason is genetic? Can anyone tell why India is not yet affected with Covid-19?
- poilcn 7y agoNo testing = no information. In regard of Iran, a cynic could say that they have political motivation to stress on the pandemic. Not long time ago they had riots.
- roenxi 7y agoThe odds are excellent that India has a large infected population but haven't reported any statistics to WHO or whatever they need to do to get the numbers into the English speaking press.
- pcr0 7y agoInfected persons are easy to cover up with inadequate testing as we've seen in the US but deaths are much harder to hide as we've seen in China and Iran. There's neither in India currently so I'd say there is no sustained local outbreak in India yet.
- pcr0 7y agoLocal community outbreaks are a matter of probability based on travel connections with countries that have outbreaks. I believe Italy and Iran have closer economic ties and more travel volume to China than India. https://www.wired.com/story/covid-19-is-traveling-along-the-new-silk-road/ https://www.wired.com/story/covid-19-is-traveling-along-the-...
- chx 7y agoAs I noted elsewhere in this thread: read David Reich's Who We Are and How We Got Here. To quote: > 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/ 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.
- coronavirus 7y agoI was taught race was skin deep, a social construct?
- martingoodson 7y agoThis title does not accurately represent the findings of this article/letter. It should be changed to something less misleading - like the original title.
- username90 7y agoWhy was this title used when the numbers showed that Europeans are typically even lower than Africans? If this is true then Covid-19 is unlikely to be a problem outside of Asia, most likely it has already spread far and wide and we aren't noticing since we expect similar rate of problematic cases as in China.
- hirenj 7y agoI just spent a few minutes reading up on this. 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!
- knolax 7y agoAs other have pointed out, this isn't a scientific paper and it isn't peer reviewed. In addition, the title is editorialized to state something the article itself doesn't support strongly: 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%2Fs41421-020-0147-1/MediaObjects/41421_2020_147_MOESM3_ESM.xlsx https://static-content.springer.com/esm/art%3A10.1038%2Fs414... Mods: Please change the submission title to the actual article title.
- bibabaloo 7y agoHas there been anything published about corona virus cases per ethnicity? Or many confirmed cases of people of non Asian ethnicity getting it?