
The major genetic risk factor for severe Covid-19 is inherited from Neandertals - drocer88
https://www.biorxiv.org/content/10.1101/2020.07.03.186296v1
======
herf
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_...](https://you.23andme.com/tools/data/?query=rs10490770&filter_by_platforms=true)

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

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

~~~
drocer88
Try this :
[https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?do_not...](https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?do_not_redirect&rs=rs10490770)

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.

------
drocer88
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](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...](https://genome.ucsc.edu/cgi-
bin/hgTracks?db=hg19&position=chr3%3A45871908%2D45909024)

The genome wide association study that points out this area of the genome is
here :
[https://www.nejm.org/doi/full/10.1056/NEJMoa2020283](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
Also only ~4% in the US, and virtually absent in Africa.

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

~~~
roywiggins
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.

~~~
ethanwillis
I mean.. China's official numbers are around 84k infected.. and much less dead
than that. So...

~~~
ashtonkem
The “count the bodies” technique is meant for situations where the country
can’t test for COVID, either because it was too early or they don’t have the
infrastructure. That technique won’t work on countries just willing to lie
about it.

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Standard disclaimer that this is a preprint that has not been peer reviewed.

------
gorkish
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.

------
boberto123
[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?

------
not2b
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
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

~~~
drocer88
Other factors may be obesity (
[https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvl...](https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=25)
) , diabetes (
[https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvl...](https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=18))
and Vitamin D deficiency ( [http://www.cooperinstitute.org/2019/09/24/african-
americans-...](http://www.cooperinstitute.org/2019/09/24/african-americans-at-
greatest-risk-of-vitamin-d-deficiency) ).

~~~
IncRnd
What underlies all of that is the strength of the immune system, which will be
low for many diets and lifestyles.

------
tbinmd
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?

~~~
boberto123
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...](https://www.gnxp.com/WordPress/2020/07/04/using-23andme-ancestry-
family-tree-dna-to-identify-risk-allele-for-respiratory-failure-with-
covid-19/comment-page-1/)

=== 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.

