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Genetic Risk Factor for Covid-19

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Plumster
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Genetic Risk Factor for Covid-19

Postby Plumster » Wed Apr 08, 2020 7:50 am

Hi all,

Nutrahacker is offering a free report on a risk allele for Covid-19: rs2070788. The risk allele is G.

Here's what they say:
Disclaimer: This report is offered for free by Nutrahacker, LLC. It is not intended to diagnose, treat, or prevent any disease. It is for informative and educational purposes only. Please follow the advice of your healthcare provider.

ACE2 has been shown to be the receptor for COVID-19 (1). This is the same receptor identified and used by the closely related viruses SARS and H1N1 (2,3). It follows that higher levels of ACE2 would be implicated in poorer disease outcomes, however no SNPs in the ACE2 have been shown to have an effect in the severity of SARS (4).

ACE2 is cleaved (cut) by two different enzymes. Cleavage by one enzyme in particular, TMPRSS2, appears to make the protein susceptible to viral attack (5). TMPRSS2 and ACE2 colocalize (6). Blocking TMPRSS2 appears to be a treatment modality (7).

Polymorphisms in TMPRSS2 affect severity of H1N1 (8) by increasing infectivity of the virus. Hence, it is likely that related viruses using the same entry path will have a similar response to these polymorphisms. Rs2070788 (G overrepresented in high severity cases, GG 2-fold risk of high severity disease), this polymorphism is probably tagging to rs383510. Higher expression of gene is higher severity of H1N1. rs38310 T allele enhances activity of the gene. These polymorphisms are not independent, so just one is needed to assess the activity of TMPRSS2.
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR

GemmaJ
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Re: Genetic Risk Factor for Covid-19

Postby GemmaJ » Sat Apr 25, 2020 5:10 am

I'm just wondering if anyone has used this service? I'm umming and arring over uploading my raw data.....

GemmaJ
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Re: Genetic Risk Factor for Covid-19

Postby GemmaJ » Sat Apr 25, 2020 6:10 am

So if my genotype is A/G: 1/2, I'm at risk, correct? I think that's right - no Gs means lower risk, one G higher risk and 2 Gs higher risk again...

Tincup
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Re: Genetic Risk Factor for Covid-19

Postby Tincup » Sat Apr 25, 2020 12:29 pm

So I did it. Interestingly the report shows rs2070788 as AG while a search of the raw .txt file or my Promethease report for rs2070788 comes up empty. So I wonder where their report gets the AG?
Tincup
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GemmaJ
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Re: Genetic Risk Factor for Covid-19

Postby GemmaJ » Sat Apr 25, 2020 2:00 pm

I don't know why I didn't think of browsing my 23andme raw data in the first place. Just did and it confirms I'm AG. Weird about Promethease...Wish I had some good idea about how that could of happened but can't think of one. On 23andme the name of the gene is TMPRSS2 and rs2071788 is the SNP but I'm very amateur at this so guessing you know that already. Maybe search Promethease for TMPRSS2?

Tincup
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Re: Genetic Risk Factor for Covid-19

Postby Tincup » Sat Apr 25, 2020 3:17 pm

GemmaJ wrote: Maybe search Promethease for TMPRSS2?

This is what I get when I do that: rs12329760(C;T)
Tincup
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GemmaJ
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Re: Genetic Risk Factor for Covid-19

Postby GemmaJ » Sun Apr 26, 2020 1:52 am

This is what I get when I do that: rs12329760(C;T)


Which is a different variant of that gene. Weird - seems Promethease didn't genotype the rs2070788 variant for you so I have no idea how Nutrahacker managed to come back with a result...? Sorry, I'm no help at all :roll:

Tincup
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Re: Genetic Risk Factor for Covid-19

Postby Tincup » Sun Apr 26, 2020 6:19 am

GemmaJ wrote:Weird - seems Promethease didn't genotype the rs2070788 variant for you so I have no idea how Nutrahacker managed to come back with a result...?


I got this email from Nutrahacker - maybe imputed??? I downloaded the 395 MB file, which has like ~20 compressed files. I've not explored, yet...

Hey there Nutrahacker, your imputed genome results are ready!
You now have access to over 30 million locations in your genetic code.
Click here to access your imputation results

The imputation results will be available for free during the next 24 hours only.
Tincup
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GemmaJ
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Re: Genetic Risk Factor for Covid-19

Postby GemmaJ » Sun Apr 26, 2020 12:04 pm

Ooohhh - Let me know if it's useful as I got that email as well but as I'd already got the information I needed I didn't explore any further. Sometimes I think I can know too much!!

Tincup
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Re: Genetic Risk Factor for Covid-19

Postby Tincup » Sun Apr 26, 2020 12:18 pm

GemmaJ wrote:Ooohhh - Let me know if it's useful as I got that email as well but as I'd already got the information I needed I didn't explore any further. Sometimes I think I can know too much!!


Note, when uncompressed they all have a file extension of .vcf. This extension is also used for contacts in an address book. Obviously not the same format! The first file may have some utility. The second, not so much for me as no RS#'s listed. A vcf file reader would be helpful, though you can look at them like the below in a text editor. Likely more than I care about...

There are many more files I've yet to open.

First lines of one file:

##fileformat=VCFv4.2
##filedate=20200425
##source="beagle.25Nov19.28d.jar"
##INFO=<ID=AF,Number=A,Type=Float,Description="Estimated ALT Allele Frequencies">
##INFO=<ID=DR2,Number=1,Type=Float,Description="Dosage R-Squared: estimated squared correlation between estimated REF dose [P(RA) + 2*P(RR)] and true REF dose">
##INFO=<ID=IMP,Number=0,Type=Flag,Description="Imputed marker">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=DS,Number=A,Type=Float,Description="estimated ALT dose [P(RA) + 2*P(AA)]">
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT ci_d682aa54-5f87-4d6d-ac2c-7f8ee502a3ce_positions.txt.sorted
12 60219 rs371828716 G A . PASS DR2=0.00;AF=0.0007;IMP GT:DS 0|0:0
12 60317 rs566046722 C T . PASS DR2=0.00;AF=0.0038;IMP GT:DS 0|0:0.01
12 60473 rs112712197 C T . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60474 rs537376773 G A . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60492 rs558711391 T A . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60654 rs574457226 G A . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60663 rs541837560 T C . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60734 rs557042443 G A . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 60760 rs572097088 C CA . PASS DR2=0.00;AF=0.1971;IMP GT:DS 0|0:0.39
12 60918 rs532304191 C CA . PASS DR2=0.08;AF=0.1757;IMP GT:DS 0|0:0.35
12 61107 rs186362565 G T . PASS DR2=0.00;AF=0.0015;IMP GT:DS 0|0:0
12 61161 rs569750441 A G . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
12 61172 rs535178008 G A . PASS DR2=0.00;AF=0.0042;IMP GT:DS 0|0:0.01
12 61329 rs575274757 C T . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0

Another
##fileformat=VCFv4.2
##filedate=20200425
##source="beagle.25Nov19.28d.jar"
##INFO=<ID=AF,Number=A,Type=Float,Description="Estimated ALT Allele Frequencies">
##INFO=<ID=DR2,Number=1,Type=Float,Description="Dosage R-Squared: estimated squared correlation between estimated REF dose [P(RA) + 2*P(RR)] and true REF dose">
##INFO=<ID=IMP,Number=0,Type=Flag,Description="Imputed marker">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=DS,Number=A,Type=Float,Description="estimated ALT dose [P(RA) + 2*P(AA)]">
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT ci_d682aa54-5f87-4d6d-ac2c-7f8ee502a3ce_positions.txt.sorted
X 60020 . T TA,TAAC . PASS DR2=0.00,0.00;AF=0.0011,0.0130;IMP GT:DS 0|0:0,0.03
X 60026 . T C . PASS DR2=0.00;AF=0.0043;IMP GT:DS 0|0:0.01
X 60032 . T C . PASS DR2=0.00;AF=0.0043;IMP GT:DS 0|0:0.01
X 60034 . ACC AC,A . PASS DR2=0.00,0.00;AF=0.0000,0.0665;IMP GT:DS 0|0:0,0.13
X 60052 . T A . PASS DR2=0.00;AF=0.3644;IMP GT:DS 0|0:0.73
X 60060 . G C . PASS DR2=0.00;AF=0.0111;IMP GT:DS 0|0:0.02
X 60069 . T A . PASS DR2=0.00;AF=0.3644;IMP GT:DS 0|0:0.73
X 60071 . G A . PASS DR2=0.00;AF=0.0045;IMP GT:DS 0|0:0.01
X 60072 . G C . PASS DR2=0.00;AF=0.0034;IMP GT:DS 0|0:0.01
X 60072 . G C,T . PASS DR2=0.00,0.00;AF=0.0048,0.0809;IMP GT:DS 0|0:0.01,0.16
X 60112 . G C . PASS DR2=0.00;AF=0.0251;IMP GT:DS 0|0:0.05
X 60116 . C T . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
X 60153 . C G . PASS DR2=0.00;AF=0.0000;IMP GT:DS 0|0:0
X 60181 . G C . PASS DR2=0.00;AF=0.0023;IMP GT:DS 0|0:0
X 60184 . A G . PASS DR2=0.00;AF=0.0185;IMP GT:DS 0|0:0.04
X 60185 . T C . PASS DR2=0.00;AF=0.4499;IMP GT:DS 0|0:0.9
Tincup
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