COVID-19 Host Genetics analysis

As a part of COVID-19 Host Genetics Initiative, we perform the following set of analyses to better understand the genetic basis of COVID-19 susceptibility and severity.

Please check out initial draft of host genetics of COVID-19, Initial review and analysis of COVID-19 host genetics and associated phenotypes.

• HLA: HLA frequency in UK Biobank[2].
• ABO: The ABO blood type frequency in UK Biobank.
• snpnet: Polygenic prediction of biomarkers and blood measurements. We deposit notebooks and scripts for polygenic risk score (PRS) analysis in this directory[3,4,5].
• PRS_PheWAS: Application of blood measurement PRSs for disease risk prediction.

Please share ABO blood type frequency in COVID-19 patients

We replicated recent findings in Zhao et al.[6] about the significant risk reduction of the blood group O across different control groups in UK Biobank. For a robust inference of risk factors, we would like to encourage a broad sharing of ABO blood type frequencies across (1) mild, (2) moderate, and (3) severe/critical COVID-19 cases at https://tinyurl.com/abo-covid19.

Publicly available resources

• PRS-PheWAS results
• ABO blood type frequencies in UK Biobank
• HLA allelotype frequencies in 17th IHIW NGS HLA Data and UK Biobank
• The weights for polygenic risk prediction
  • The weights of PRSs are available at Google Drive shared folder: https://bit.ly/rivas-lab_covid19_PRS_weights.
  • Please see the documentation in snpnet directory for more information.
• We developed HLA/ABO frequency map for visualization of the ABO bloodtype and HLA allelotype frequency data.

Note

This repo is a summary of joint effort for the community project from the Stanford Researchers and Clinicians, including (but not limited to) the following people: Yosuke Tanigawa, Kazutoyo Osoegawa, Marcelo Fernandez Vina, Euan Ashley, Carlos Bustamante, Julia Palacios, Benjamin Pinsky, Manuel A. Rivas.

Acknowledgement

We thank Dr. Kazutoyo Osoegawa for reformatting and aggregation of the 17th IHIW NGS HLA Data. We thank Stanford Research Computing Center for providing prioritized queue for COVID-19 research[7].

Update log

• 2020/4/22: We make UK Biobank analysis and summary statistics publicly available.
• 2020/4/3: We added summary for normalization of PRS.
• 2020/4/1: We released the updated PRS weights. Please see snpnet directory for more information.
• 2020/3/29: We added two-digit HLA allelotype frequency information.
• 2020/3/28: We updated the HLA allelotype frequencies dataset. It now includes the HLA allelotype frequencies across more than 100 countries/regions from UK Biobank, in addition to the 17th IHIW NGS HLA Data. We launched the HLA map app for vidualization of the frequency data.
• 2020/3/27: Our preprint[1] is introduced in a news article in Science.
• 2020/3/26: We updated the link to COVID-19 Host Genetics Initiative.
• 2020/3/26: We added aggregated summary of Global frequencies of HLA allelotypes from the 17th IHIW NGS HLA Data in HLA. We thank Dr. Kazutoyo Osoegawa for reformatting and aggregation of the data. We updated the directory name of HLA from UKB_HLA_freq.
• 2020/3/24: Our initial draft write-up is now posted on preprints.org.
• 2020/3/23: We added PRS evaluation plots and updated the documentation.
• 2020/3/22: We added results and source code for the PRS-PheWAS analysis PRS_PheWAS.
• 2020/3/22: We updated the documentation of the ABO blood type analysis.
• 2020/3/22: We made our initial draft of our host genetic analysis, Initial review and analysis of COVID-19 host genetics and associated phenotypes available at ~~Google Docs~~ (it is now available at Preprints.org).
• 2020/3/21: We added the ABO blood type frequency reference across 9 population groups in UK Biobank (White British, Non-British white, African, South Asian, East Asian, self-reported Chinese, self-reported Indian, self-reported Pakistani, and self-reported Bangladeshi).
• 2020/3/20: We added a link to the 17th IHIW NGS HLA Data.
• 2020/3/19: We made an initial release of the polygenic risk score weights for 66 triats (blood measurements and biomarkers)! The weights of polygenic risk scores (PRSs) are available at Google Drive shared folder: https://bit.ly/rivas-lab_covid19_PRS_weights. Please see snpnet directory for more information. We are still running the PRS computations and we will make an update release when we have improved results.
• 2020/3/17: We updated the HLA fequency reference. It now includes the frequencies from 5 population groups.
• 2020/3/17: initial release!

Reference

1. Tanigawa, Y. & Rivas, M. Initial Review and Analysis of COVID-19 Host Genetics and Associated Phenotypes. Preprints.org (2020).
2. McInnes, G. et al. Global Biobank Engine: enabling genotype-phenotype browsing for biobank summary statistics. Bioinformatics (2019).
3. Qian, J. et al. A Fast and Flexible Algorithm for Solving the Lasso in Large-scale and Ultrahigh-dimensional Problems. bioRxiv 630079 (2019).
4. Sinnott-Armstrong, N. et al. Genetics of 38 blood and urine biomarkers in the UK Biobank. bioRxiv 660506 (2019).
5. UK Biobank : Category 100081. Blood count - Blood assays - Assay results - Biological samples.
6. Zhao, J. et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. medRxiv 2020.03.11.20031096 (2020).
7. Sherlock joins the fight against COVID-19. Stanford Research Computing Center.
8. Kaiser, J. How sick will the coronavirus make you? The answer may be in your genes. Science (News article) (2020).