The MTCOJO app performs multi-trait conditional and joint analysis. It conditions a harmonised target GWAS study on one harmonised covariate GWAS study.
Use MTCOJO when you want to assess the target study’s association results after accounting for the genetic effects of a related covariate trait.
The app uses a user-selected LD reference, either European ancestry (EUR) or a combined all-ancestry (ALL) reference.
Before you begin
You will need:
- A harmonised target GWAS study
- A harmonised covariate GWAS study
- An appropriate LD-reference choice
- A project in which to save the job and results
Name your job
Enter a descriptive name in the Prefix field. This is required.
[Screenshot 1: Red box around the Prefix field.]
For example:
BMI_conditioned_on_T2DCAD_conditioned_on_LDLHeight_adjusted_for_BMI
Select the target study
Use Target Study to select the GWAS study whose association results you want to condition.
[Screenshot 2: Red box around the Target Study dropdown.]
The target study is the primary GWAS dataset that will be adjusted for the selected covariate.
Select the covariate study
Use Covariate Study to select the GWAS study used for conditioning.
[Screenshot 3: Red box around the Covariate Study dropdown.]
The covariate should represent a trait that may contribute to, overlap with, or confound genetic associations in the target study.
Choose effect allele frequency sources
Use Use Target EAF From and Use Covariate EAF From to specify the source of effect allele frequency (EAF) information for each study.
[Screenshot 4: Highlight both EAF dropdowns, showing the default “study” selection.]
The default setting, study, uses EAF information from the corresponding harmonised study. Change this only when your analysis protocol requires an alternative source.
Accurate EAF information supports reliable allele alignment and conditional analysis.
Set the COJO P-value threshold
Use COJO P-value Threshold to define the statistical-significance threshold used in the conditional analysis. The default is 5e-8.
[Screenshot 5: Red box around the COJO P-value Threshold field.]
The default retains genome-wide significant association signals. Adjust this only if your analysis plan specifies a different threshold.
Set the MAF floor
Use MAF Floor to specify the minimum minor allele frequency for variants included in the analysis. The default is 0.01.
[Screenshot 6: Red box around the MAF Floor field.]
Variants below this threshold may be excluded because low-frequency variants can provide less stable estimates.
Complete the remaining configuration fields
Scroll down to review and complete all remaining required settings, including the LD-reference selection and destination project.
[Screenshot 7: Add a screenshot of the lower section of the MTCOJO form. Highlight the LD-reference field, Project selector, and “Launch App” button.]
Select an LD reference appropriate to the ancestry represented in the GWAS data:
- Choose EUR for primarily European-ancestry data.
- Choose ALL when the combined all-ancestry reference is appropriate for your analysis.
Launch the analysis
Review the target study, covariate study, EAF sources, thresholds, LD reference, and project. Then select Launch App.
The conditional-analysis results will be available from the selected project or the job results area when processing is complete.
Tips
- The target and covariate studies should be harmonised and suitable for comparison.
- Choose an LD reference that best represents the ancestry of the GWAS data.
- Ensure the target and covariate represent distinct traits with a clear rationale for conditioning.
- MTCOJO adjusts genetic association results statistically; interpret findings alongside trait biology, sample overlap considerations, and other supporting analyses.