The major genetic risk factor for severe Covid-19 is inherited from Neandertals

https://www.biorxiv.org/content/10.1101/2020.07.03.186296v1

by drocer88 • 6 years ago

51 28 6 years ago

zrail• 6 years ago

Standard disclaimer that this is a preprint that has not been peer reviewed.

drocer883• 6 years ago

Svante Pääbo , one of the preprint authors, is the head of the Max Planck Institute for Evolutionary Anthropology. https://en.wikipedia.org/wiki/Svante_P%C3%A4%C3%A4bo . He is known for his work in assembling the Neanderthal and Denisovan genomes.

Of particular note in this paper, the genetic variants in the genomic locus discussed are found in 30% of South Asian populations: India and Bangladesh. The highest frequency occurs in Bangladesh, where more than half the population (63%) carries at least one copy of the Neandertal risk variant and 13% is homozygous for the variant. The risk variant is 8% frequency in Europe.

The hg19 location of Genetic variants in LD (r2>0.99) with rs11385942 in Eurasian populations can be viewed here at the UCSC genome browser: https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&position=ch...

The genome wide association study that points out this area of the genome is here : https://www.nejm.org/doi/full/10.1056/NEJMoa2020283 . At this "locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1."

Three of the genes, XCR1 CXCR6 CCR9, are involved with chemokine receptor activity and G-protein coupled chemoattractant receptor activity.

mirimir• 6 years ago

Also only ~4% in the US, and virtually absent in Africa.

rossdavidh• 6 years ago

"Here, we show that the risk is conferred by a genomic segment of ~50 kb that is inherited from Neandertals and occurs at a frequency of ~30% in south Asia and ~8% in Europe."

Hmmm...thus far, the mortality per capita from Covid-19 has been much higher in Europe, especially western Europe, than in south Asia. Not saying that couldn't change, but the weekly mortality peaks in western Europe were literally an order of magnitude higher than for Bangladesh, India, or Pakistan. So either this finding is flawed in some way, or (perhaps more likely) even the biggest genetic risk factor for severe Covid-19 is not that big of a factor, and what's going on is mostly not genetic.

slicktux• 6 years ago

Or maybe the stats used for the data in European countries are flawed...or there is less testing in the latter countries....

roywiggins• 6 years ago

You don't need testing, just accurate body counts. You can see COVID hit Europe as a spike in excess deaths, even if you weren't testing. If there were currently a mortality spike in Bangladesh even higher than Europe's, it would not go unnoticed. Disappearing bodies is not that easy.

herf• 6 years ago

If you have 23andme, the exact allele is not on the chip. However, a different allele is strongly associated with the region:

https://you.23andme.com/tools/data/?query=rs10490770&filter_...

The major A/A variant is listed as T/T on 23andme. If you have a result other than "T/T", you're likely to be in the high-risk group.

refs: https://www.snpedia.com/index.php/Rs11385942 [not on 23andme] https://www.snpedia.com/index.php/Rs10490770

modeless• 6 years ago

That 23andme link doesn't work for me, it says no genes or markers found for rs10490770.

drocer883• 6 years ago

Try this : https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?do_not...

This breaks down the population frequencies. Of note: the HAPMAP AA frequencies: Gujarati Indians in Houston Texas : 38% , African ancestry in Southwest USA: 4%. It is absent in Chinese, Japanese and sub-saharan Africans.

helpme232• 6 years ago

I couldn’t get it to work either, did anyone figure out how to view it on there?

LegitShady• 6 years ago

This is actually the first time the 23andme results did anything useful for me. Thank!

helpme232• 6 years ago

How did you get it to pull on 23 and me. I have more Neanderthal variants than 99% of users so I’m super interested. Thank you for any help you can provide.

wcoenen• 6 years ago

Thanks for sharing these pointers!

A caveat for those who don't click through to the snpedia references: the "strongly associated region" only correlates well for Caucasians.

not2b• 6 years ago

But how can this be, given that African-Americans, with far less Neanderthal ancestry than European-Americans, are dying of COVID-19 at a much higher rate in the US?

xikrib• 6 years ago

Given that there's a strong correlation between race and poverty in the US (via racism) and a strong correlation between poverty and infection rate which, it seems to mean poverty is a greater indicator than genetics. After all the genetic factor only comes into play after exposure, while poverty increases the likelyhood of exposure

drocer883• 6 years ago

Other factors may be obesity ( https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvl... ) , diabetes ( https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvl...) and Vitamin D deficiency ( http://www.cooperinstitute.org/2019/09/24/african-americans-... ).

jjtheblunt• 6 years ago

is NYC with its highest rate of cases in the USA a generalization: density of people (which happens in poverty and in opulence, for different reasons) increases likelihood of exposure?

smt88• 6 years ago

The genetic risk is one factor. There are many others. In the case of Americans of African descent, the other factors have a much stronger effect.

pnako• 6 years ago

There are many risk factors, not just this one.

Kednicma• 6 years ago

Maybe genetics aren't a very important part of mortality risk.

gorkish• 6 years ago

I do not have any particular comment on this gene or the topic of COVID-19, but I have a related question for the experts out there.

Let's say I were to send off to Dante labs and get my entire genome sequenced. Given emerging research like this where someone says "we have identified this specific gene that does so-and-so," does the average geek have any hope of being able to determine if they have a copy of that gene? Or does that type of interpretation require the effort of a trained expert?

How close are we to receiving a personalized genetic vulnerability feed? I'm sure the hypochondriacs out there would sign up in a heartbeat.

tbinmd• 6 years ago

So in my 23andme it shows me as having the T/T genotype of this marker. Does that mean I do or do not have the at risk marker?

boberto1232• 6 years ago

I think you're good. From what I've read, the high risk is C. T/T is modern human. C is neanderthal. So C/C - youre 3 times more likely to get sick. C/T youre 1.5times more likely to get sick.

Reference: https://www.gnxp.com/WordPress/2020/07/04/using-23andme-ance...

=== If this is wrong, someone correct me, but T/T results from 23andme seem to be 84.5% of the population (caucasion people), so YOU SHOULD BE FINE.

boberto1232• 6 years ago

[Sars-Cov-2][Outcome risk] rs10490770 (Caucasisn only)

Risk: AG, GG (~15.5% of population?)

Safe: AA (~84.5% of population?)

--- SO, if 23andme says its T/T and its actually A/A(as herf said), than 84.5% of the population would have T/T via 23andme. I am confused then. If I have T/T through 23andme, am I at higher risk when ~85% of the population has the same thing?

The major genetic risk factor for severe Covid-19 is inherited from Neandertals

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