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

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  1. #1
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    SARS-CoV-2 respiratory failure: risk SNPs, Bloodtype A is a risk, O is protective

    The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis
    Abstract
    Background. Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients. Methods. We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels. Results. We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). Conclusions. We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.

    rs657152 is covered by 23andMe but not Ancestry DNA.
    A is the risk variant.
    C is non-risk variant.

    rs11385942 is not covered by 23andMe or Ancestry.

    I am AA for rs657152, my blood type is AB+.
    rs11385942 does not appear in any of (numerous) WGS so I probably have the reference variant, which is non-risk.

    I have not to my knowledge had SARS-CoV-2.

    Please feel free to post your test results in this thread. As well as any other references to published DNA/SARS-CoV-2 associations.
    Last edited by pmokeefe; 06-04-2020 at 08:50 PM.
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  3. #2
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    According to 23andme my blood type is A+ but my result at rs657152 is AC. Not sure what to make of this then.

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    Quote Originally Posted by J Man View Post
    According to 23andme my blood type is A+ but my result at rs657152 is AC. Not sure what to make of this then.
    That's interesting. One of family members is also AC for rs657152 on 23andMe but believes they have blood type B. I'm not sure of the correlation between rs657152 and ABO blood type, it would be interesting to find out.
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    The major genetic risk factor for severe COVID-19 is inherited from Neandertals

    The major genetic risk factor for severe COVID-19 is inherited from Neandertals
    Hugo Zeberg and Svante Pääbo

    Abstract
    A recent genetic association study (Ellinghaus et al. 2020) identified a gene cluster on chromosome 3
    as a risk locus for respiratory failure in SARS-CoV-2. Recent data comprising 3,199 hospitalized
    COVID-19 patients and controls reproduce this and find that it is the major genetic risk factor for
    severe SARS-CoV-2 infection and hospitalization (COVID-19 Host Genetics Initiative). 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.
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    Quote Originally Posted by J Man View Post
    According to 23andme my blood type is A+ but my result at rs657152 is AC. Not sure what to make of this then.
    It tells you your blood type?
    Ancestry DNA: Eng/Wales/NW Europe 56%, Ireland/Scotland: 28%, Norway 11%, Germanic Europe 3%, French 2%
    - Communities: SW Quebec French Settlers (Vaudreuil-Solanges, Rivičre ŕ la Graisse, and Outaouais & Laurentides French Settlers) and So. Ontario Settlers (W & Cen. Ontario Settlers)
    Ancestry as I was told: Irish, Scottish, English, French, German

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    Quote Originally Posted by Avrowolf View Post
    It tells you your blood type?
    23andMe no longer reports blood type, though it did in the past.
    Editor’s note 7/23/20: Thanks to all our readers for their questions on this post. Please note, 23andMe does not currently offer a report on blood type.
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    Covid-19 Respiratory failure SNP for Ancestry DNA testers

    For those with Ancestry DNA but not 23andMe.

    rs8176719 is in linkage disequilibrium with rs657152 (the SNP mentioned in the paper).
    The pairwise linkage disequilibrium coefficient D'=1.0 for rs657152,rs8176719 for Population: 1000GENOMES:phase_3:GBR
    However D' is not 1.0 for all populations. Check LD for different populations here: https://ldlink.nci.nih.gov/?tab=ldmatrix

    I is the risk value, D is nonrisk value on Ancestry.
    This is the line from my Ancestry raw file
    rs8176719 9 136132908 I I

    I checked another person who was CA for 23andMe for rs657152 and they were DI for rs8176719 on Ancestry, which is consistent.

    There are other SNPs that are in LD with rs657152 (the SNP mentioned in the paper) rs8176719 happened to be the first one that I found on Ancestry, there may be others.
    Last edited by pmokeefe; 06-05-2020 at 04:26 AM.
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    RS 657152 AC
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    Would say I'm definitely in the 'at risk for poor outcome' category due to being overweight . A situation caused by antipsychotics . However, as is typical re the way those of us with SMI are regarded, being on anti psychotics isn't flagged as a risk factor .
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    I am blood type O-, rs657152 CC.
    However, just noticed in the Promethease report rs35705950(G;T)
    Possible miscall in Ancestry v2d data; otherwise, moderately (>5x) higher risk for lung issues (fibrosis or pneumonia) . My result is from 23andMe.

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