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Thread: SARS-CoV-2 respiratory failure: risk SNPs, Bloodtype A is a risk, O is protective

  1. #101
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    I looked up the two main SNP in the UK Biobank data on COVID 19 deaths (364 COVID-19 deaths vs. 486,956 negative/unknown UKBB control).

    rs13078854 Beta 0.454 p-value 0.00192 odds ratio 1,575
    rs8176645 Beta 0.105 p-value 0.24990 odds ratio 1,101

    rs8176645 is the best proxy I found for chr9 rs9411378 ABO gene. Like the other proxies, it is not even nominally significantly associated with COVID 19 death vs. population.
    I'd say that the chromosome 3 hit on severity is reflected in the death analysis, but the OR of ~1,6 is comparable or even lower than the odds of being hospitalized with severe disease from the Ellinghaus or 23andme paper. Overall, it doesn't reach genome wide significance for death as an outcome, but probably would in a larger analysis.
    A number of other positions do, like the APOE locus rs429358, which codes for the APOE ∊3 and APOE ∊4 alleles with an OR of 1,45 and a p-value of 5x10^-7.

    data from here:
    https://grasp.nhlbi.nih.gov/Covid19GWASResults.aspx
    Last edited by Nive1526; 09-10-2020 at 01:33 PM.

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  3. #102
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    Quote Originally Posted by Nive1526 View Post
    I looked up the two main SNP in the UK Biobank data on COVID 19 deaths (364 COVID-19 deaths vs. 486,956 negative/unknown UKBB control).

    rs13078854 Beta 0.454 p-value 0.00192 odds ratio 1,575
    rs81766450 Beta 0.105 p-value 0.24990 odds ratio 1,101

    rs81766450 is the best proxy I found for chr9 rs9411378 ABO gene. Like the other proxies, it is not even nominally significantly associated with COVID 19 death vs. population.
    I'd say that the chromosome 3 hit on severity is reflected in the death analysis, but the OR of ~1,6 is comparable or even lower than the odds of being hospitalized with severe disease from the Ellinghaus or 23andme paper. Overall, it doesn't reach genome wide significance for death as an outcome, but probably would in a larger analysis.
    A number of other positions do, like the APOE locus rs429358, which codes for the APOE ∊3 and APOE ∊4 alleles with an OR of 1,45 and a p-value of 5x10^-7.

    data from here:
    https://grasp.nhlbi.nih.gov/Covid19GWASResults.aspx
    How did you select rs81766450 as a proxy for rs9411378?
    I just looked up rs81766450 in dbSNP, it wasn't there.
    https://www.ncbi.nlm.nih.gov/snp/?term=rs81766450
    The following term was not found in SNP: rs81766450.
    No items found.
    YFull: YF14620 (Dante Labs 2018)

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  5. #103
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    There is a zero too much, it's rs8176645. I'll edit it.

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  7. #104
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    Quote Originally Posted by pmokeefe View Post
    Trans-ethnic analysis reveals genetic and non-genetic associations with COVID-19 susceptibility and severity

    ABO: In our phenotype contrasting COVID-19 test positive individuals to test negative
    individuals, we identified an association at chr9q34.2, with index SNP rs9411378 (p-value =
    5.3e-20, C allele OR = 0.857; Figure 5).
    Another proxy for rs9411378 is rs635634. It is conservative, in the sense that it appears that people with rs635634-T are extremely likely to have rs9411378-A, which I believe is the risk variant - if I read the paper correctly.
    I checked population statistics here: https://ldlink.nci.nih.gov/?tab=ldhap.
    On the other hand, the risk variant is not covered by rs635634-T all the time - but it is for me. rs635634 was included in both my 23andMe and AncestryDNA test results.
    Generally speaking there appear to be quite a few adverse health consequences for rs635634-T https://www.ebi.ac.uk/gwas/variants/rs635634, independent of Covid19.

    Anyone else unlucky enough to have a copy of rs635634-T?
    YFull: YF14620 (Dante Labs 2018)

  8. #105
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    Quote Originally Posted by Nive1526 View Post
    There is a zero too much, it's rs8176645. I'll edit it.
    Thanks.
    BTW rs8176719, the most common variant for blood type O, is nearly identical to rs8176645 in non-Africans .
    They are not highly correlated for SSA however.
    https://ldlink.nci.nih.gov/?tab=ldhap
    YFull: YF14620 (Dante Labs 2018)

  9. #106
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    Covid-19 and Interferon

    Hidden immune weakness found in 14% of gravely ill COVID-19 patients
    By Meredith Wadman

    Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
    Some of the variants mentioned are:
    TLR3 p.Pro554Ser rs121434431 is tested at 23andMe and AncestryDNA (sometimes) the risk variant T is quite rare.

    IFNAR1 p.Pro335del rs72552343 not tested at 23andMe or AncestryDNA, risk variant is rare

    In the supplement to the paper there are two tables of variants. There are over one hundred, I have not gone through them to see if any are tested at 23andMe or AncestryDNA.
    YFull: YF14620 (Dante Labs 2018)

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