Precomputed GWAS and PheWAS

The GWAS and PheWAS tabs in ICA Cohorts allow you to visualize precomputed analysis results for phenotypes/diseases and genes, respectively. Note that these do not reflect the subjects that are part of the cohort that you created.

ICA Cohorts currently hosts GWAS and PheWAS analysis results for approximately 150 quantitative phenotypes (such as "LDL direct" and "sitting height") and about 700 diseases.

Visualize Results from Precomputed Genome-Wide Association Studies (GWAS)

Navigate to the GWAS tab and start looking for phenotypes and diseases in the search box. Cohorts will suggest the best matches against any partial input ("cancer") you provide. After selecting a phenotype/disease, Cohorts will render a Manhattan plot, by default collapsed to gene level and organized by their respective position in each chromosome.

Circles in the Manhattan plot indicate binary traits, potential associations between genes and diseases. Triangles indicate quantitative phenotypes with regression Beta different from zero, and point up or down to depict positive or negative correlation, respectively.

Hovering over a circle/triangle will display the following information:

• gene symbol

• variant group (see below)

• P-value, both raw and FDR-corrected

• number of carriers of variants of the given type

• number of carriers of variants of any type

• regression Beta

For gene-level results, Cohorts distinguishes five different classes of variants: protein truncating; deleterious; missense; missense with a high ILMN PrimateAI score (indicating likely damaging variants); and synonymous variants. You can limit results to either of these five classes, or select All to display all results together.

• Deleterious variants (del): the union of all protein-truncating variants (PTVs, defined below), pathogenic missense variants with a PrimateAI score greater than a gene-specific threshold, and variants with a SpliceAI score greater than 0.2.

• Protein-truncating variants (ptv): variant consequences matching any of stop_gained, stop_lost, frameshift_variant, splice_donor_variant, splice_acceptor_variant, start_lost, transcript_ablation, transcript_truncation, exon_loss_variant, gene_fusion, or bidirectional_gene_fusion.

• missense_all: all missense variants regardless of their pathogenicity.

• missense, PrimateAI optimized (missense_pAI_optimized): only pathogenic missense variants with primateAI score greater than a gene-specific threshold.

• missenses and PTVs (missenses_and_ptvs_all): the union of all PTVs, SpliceAI > 0.2 variants and all missense variants regardless of their pathogenicity scores.

• all synonymous variants (syn).

To zoom in to a particular chromosome, click the chromosome name underneath the plot, or select the chromosome from the drop down box, which defaults to Whole genome.

Visualize Results from Precomputed Phenome-Wide Association Studies (PheWAS)

To browse PheWAS analysis results by gene, navigate to the PheWAS tab and enter a gene of interest into the search box. The resulting Manhattan plot will show phenotypes and diseases organized into a number of categories, such as "Diseases of the nervous system" and "Neoplasms". Click on the name of a category, shown underneath the plot, to display only those phenotypes/diseases, or select a category from the drop down, which defaults to All.

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A future release of ICA Cohorts will allow you to run your own customized GWAS analysis inside ICA Bench and then upload variant- or gene-level results for visualization in the ICA Cohorts graphical user interface.