The Genome-wide MVMR Study Group app runs multivariable Mendelian randomisation (MVMR) for selected exposure studies against every study within a selected Portal study group.

Use this app when you want to run the same MVMR analysis across a set of related outcome studies, rather than selecting and running each outcome separately.

Before you begin

You will need:

• An outcome study group containing the studies you want to analyse
• Two or more exposure GWAS studies for the multivariable model
• A destination project for the job and output files

Name your job

Enter a clear Prefix to identify the analysis. You may add an optional Suffix to distinguish related runs.

[Screenshot 1: Highlight the Prefix and Suffix fields in the Job Identification section.]

For example:

• Prefix: Lipids_MVMR_outcome_group
• Suffix: GWsig_r001

Select the outcome study group

Choose the group containing your outcome studies in Outcome Study Group.

[Screenshot 2: Red box around the Outcome Study Group dropdown.]

The app runs the MVMR workflow against each study in this group as an outcome. This is useful for a phenotype panel, disease group, or other curated set of outcome studies.

Select exposure study or studies

Use Exposure Study ID to select the exposure GWAS studies to include in the multivariable model.

[Screenshot 3: Red box around the Exposure Study ID selector.]

MVMR estimates the association of each selected exposure with each outcome while accounting for the other exposures in the model.

Set the instrument P-value threshold

Use P Value Threshold to define the statistical-significance threshold for selecting genetic instruments. The default is 5e-8.

[Screenshot 4: Red box around the P Value Threshold field.]

The default retains genome-wide significant variants. Change this only if your analysis plan requires a different instrument-selection threshold.

Set the LD threshold

Use R2 Threshold to define the maximum allowed LD between selected variants. The default is 0.001.

[Screenshot 5: Red box around the R2 Threshold field.]

A lower R2 threshold retains more independent genetic instruments. The default value is stringent and commonly used for genome-wide MR analyses.

Select a project

Choose the destination project in the Project dropdown. This is required.

[Screenshot 6: Red box around the Project dropdown.]

The analysis jobs and output files will be saved to this project.

Select the effect model

Choose an option in Effect Model. This is required.

[Screenshot 7: Red box around the Effect Model dropdown, showing the default “fixed” setting.]

The default fixed model should be retained unless your analysis protocol specifies another model. Use a different effect model only when it is appropriate for your study design and planned interpretation.

Launch the workflow

Review the outcome study group, exposure studies, thresholds, project, and effect model. Then select Launch App.

[Screenshot 8: Red box and arrow pointing to “Launch App”.]

The app runs an MVMR analysis for each eligible outcome study in the selected group. When complete, access the outputs from the selected project or the job results area.

Tips

• Use this app when the same exposures need to be screened across many outcome studies.
• Review the composition of the outcome group before launching; every study in the group will be included as an outcome.
• Use a meaningful prefix and suffix to distinguish runs across different outcome groups or exposure sets.
• Ensure that the selected exposures are appropriate to model together and have sufficient genetic instruments.