COVID GWAS v4 Track Settings
 
COVID risk variants from GWAS meta-analyses by the COVID-19 Host Genetics Initiative (Rel 4, Oct 2020)   (All COVID-19 tracks)

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 Severe COVID vars  Severe respiratory COVID risk variants from the COVID-19 HGI GWAS Analysis A2 (4336 cases, 12 studies, Rel 4: Oct 2020)   Schema 
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 Hosp COVID vars  Hospitalized COVID risk variants from the COVID-19 HGI GWAS Analysis B2 (7885 cases, 21 studies, Rel 4: Oct 2020)   Schema 
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 Tested COVID vars  Tested COVID risk variants from the COVID-19 HGI GWAS Analyis C1 (11085 cases, 20 studies, Rel 4: Oct 2020)   Schema 
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 All COVID vars  COVID risk variants from the COVID-19 HGI GWAS Analysis C2 (17965 cases, 33 studies, Rel 4: Oct 2020)   Schema 

Description

This track set shows the results of the GWAS Data Release 4 (October 2020) from the COVID-19 Host Genetics Initiative (HGI): a collaborative effort to facilitate the generation of meta-analysis across multiple studies contributed by partners world-wide to identify the genetic determinants of SARS-CoV-2 infection susceptibility, disease severity and outcomes. The COVID-19 HGI also aims to provide a platform for study partners to share analytical results in the form of summary statistics and/or individual level data of COVID-19 host genetics research. At the time of this release, a total of 137 studies were registered with this effort.

The specific phenotypes studied by the COVID-19 HGI are those that benefit from maximal sample size: primary analysis on disease severity. For the Data Release 4 the number of cases have increased by nearly ten-fold (more than 30,000 COVID-19 cases and 1.47 million controls) by combining data from 34 studies across 16 countries.

The four tracks here are based on data from HGI meta-analyses A2, B2, C1, and C2, described here:

Due to privacy concerns, these browser tracks exclude data provided by 23andMe contributed studies in the full analysis results. The actual study and case and control counts for the individual browser tracks are listed in the track labels. Details on all studies can be found here.

Display Conventions

Displayed items are colored by GWAS effect: red for positive (harmful) effect, blue for negative (protective) effect. The height ('lollipop stem') of the item is based on statistical significance (p-value). For better visualization of the data, only SNPs with p-values smaller than 1e-3 are displayed by default.

The color saturation indicates effect size (beta coefficient): values over the median of effect size are brightly colored (bright red    , bright blue    ), those below the median are paler (light red    , light blue    ).

Each track has separate display controls and data can be filtered according to the number of studies, minimum -log10 p-value, and the effect size (beta coefficient), using the track Configure options.

Mouseover on items shows the rs ID (or chrom:pos if none assigned), both the non-effect and effect alleles, the effect size (beta coefficient), the p-value, and the number of studies. Additional information on each variant can be found on the details page by clicking on the item.

Methods

COVID-19 Host Genetics Initiative (HGI) GWAS meta-analysis round 4 (October 2020) results were used in this study. Each participating study partner submitted GWAS summary statistics for up to four of the COVID-19 phenotype definitions.

Data were generated from genome-wide SNP array and whole exome and genome sequencing, leveraging the impact of both common and rare variants. The statistical analysis performed takes into account differences between sex, ancestry, and date of sample collection. Alleles were harmonized across studies and reported allele frequencies are based on gnomAD version 3.0 reference data. Most study partners used the SAIGE GWAS pipeline in order to generate summary statistics used for the COVID-19 HGI meta-analysis. The summary statistics of individual studies were manually examined for inflation, deflation, and excessive number of false positives. Qualifying summary statistics were filtered for INFO > 0.6 and MAF > 0.0001 prior to meta-analyzing the entirety of the data.

The meta-analysis was performed using fixed effects inverse variance weighting. The meta-analysis software and workflow are available here. More information about the prospective studies, processing pipeline, results and data sharing can be found here.

Data Access

The data underlying these tracks and summary statistics results are publicly available in COVID19-hg Release 4 (October 2020). The raw data can be explored interactively with the Table Browser, or the Data Integrator. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.

Credits

Thanks to the COVID-19 Host Genetics Initiative contributors and project leads for making these data available, and in particular to Rachel Liao, Juha Karjalainen, and Kumar Veerapen at the Broad Institute for their review and input during browser track development.

References

COVID-19 Host Genetics Initiative. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. 2020 Jun;28(6):715-718. PMID: 32404885; PMC: PMC7220587

Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD et al. Genetic mechanisms of critical illness in Covid-19. Nature. 2020 Dec 11;. PMID: 33307546