AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci

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1. 

   ScreenIT

   Mar 1, 2021

   SciScore for 10.1101/2020.10.06.20205864: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	Consent: Ethics statement: All data for this research project was from subjects who provided prior informed consent to participate in AncestryDNA’s Human Diversity Project, as reviewed and approved by our external institutional review board, Advarra (formerly Quorum). IRB: Ethics statement: All data for this research project was from subjects who provided prior informed consent to participate in AncestryDNA’s Human Diversity Project, as reviewed and approved by our external institutional review board, Advarra (formerly Quorum).
   Randomization	For all close relative pairs, one individual was randomly selected for exclusion from our study.
   Blinding	not detected.
   Power …

   SciScore for 10.1101/2020.10.06.20205864: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	Consent: Ethics statement: All data for this research project was from subjects who provided prior informed consent to participate in AncestryDNA’s Human Diversity Project, as reviewed and approved by our external institutional review board, Advarra (formerly Quorum). IRB: Ethics statement: All data for this research project was from subjects who provided prior informed consent to participate in AncestryDNA’s Human Diversity Project, as reviewed and approved by our external institutional review board, Advarra (formerly Quorum).
   Randomization	For all close relative pairs, one individual was randomly selected for exclusion from our study.
   Blinding	not detected.
   Power Analysis	not detected.
   Sex as a biological variable	35 A key recommendation in this plan is to analyze males and females separately when possible; therefore, we conducted four separate GWAS in total: susceptibility in males, susceptibility in females, hospitalization in males, and hospitalization in females.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Experimental Models: Cell Lines
   Sentences	Resources
   --psam [file that provides sex information] --covar [covariates file] --covar-name PC1, PC2, PC3, PC4, PC5, PC6, PC7, PC8, PC9, PC10, PC11, PC12, orthogonal_age, orthogonal_age2, platform --covar-variance-standardize --extract-if-info R2 >= 0.3 --freq --glm hide-covar --keep [list of unrelated Europeans] --keep-females OR keep-males --maf 0.01 --pheno [phenotype file] --pheno-name [phenotype column name]	PC2 suggested: RRID:CVCL_0483)
   Software and Algorithms
   Sentences	Resources
   Calculation of principal components to control residual population structure: After selecting unrelated individuals with European ancestry as described above, genetic PCs were calculated to include in the association studies to control residual population structure and were computed using FlashPCA 2.0.31 Input genotypes were linkage disequilibrum (LD)-pruned using PLINK 1.9 command --indep-pairwise 100 5 0.2 --maf 0.05 --geno 0.001. Imputation: Samples were imputed to the Haplotype Reference Consortium (HRC) reference panel32 version 1.1, which consists of 27,165 total individuals and 36 million variants.	PLINK suggested: (PLINK, RRID:SCR_001757)
   We determined best-guess haplotypes with Eagle version 2.4.133 and performed imputation with Minimac4 version 1.0.1.34 We used 1,117,080 unique variants as input and 8,049,082 imputed variants were retained in the final data set.	Eagle suggested: (Eagle, RRID:SCR_017262) Minimac4 suggested: None

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   Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   A key limitation of our data is that COVID-19 cases who suffered very severe or fatal infections are less likely to participate in our survey, which consequently results in undersampling cases with severe outcomes. We also restricted to individuals of European ancestry due to small sample sizes in other genetic ancestry cohorts for the susceptibility and severity outcomes in this early phase of COVID-19 survey data collection. As the COVID-19 survey cohort grows, future analyses will focus on increased ancestral diversity to increase generalizability. Finally, we lack an independent replication cohort for our novel findings and will rely on future ascertainment of additional survey respondents and COVID-19 GWAS consortia27 efforts to determine whether our findings are reproducible. In summary, we collected over 500,000 self-reported COVID-19 outcomes in under two months and conducted one of the largest genetic studies of infection susceptibility and severity to date, thus demonstrating the value of large-scale self-reported data as a mechanism to rapidly address a serious health crisis. We identified three novel loci, all of which harbor genes with established roles in viral replication or immunity, and one of which may provide insight into why men appear to be differently affected by COVID-19 than women. We thus add to growing evidence that host genetic variation contributes to COVID-19 susceptibility and severity and suggest identification of such genetic risk factors may p...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   Results from rtransparent:

   • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
   • No protocol registration statement was detected.

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   Read the original source
2. 

   Version published to 10.1101/2020.10.06.20205864 on medRxiv

   Oct 9, 2020