Session 3: Fine-mapping and colocalization

Session Overview

Topics Covered

• What is statistical fine-mapping and how to interpret the results?
• Fine-mapping using summary statistics
• Integrating functional annotations with fine-mapping
• Colocalization and interpretation of results.

Practical

• To perform a basic fine-mapping analysis under single causal variant
• To perform a basic colocalization analysis.
• To perform fine-mapping analyses with multiple causal variants present.

Data Used

• GWAS summary statistics from Biobank Japan (BBJ) and UK Biobank
• Gene expression summary statistics from the GTEx project

Programs Used

• Sum of single effects (SuSiE): Vignette, Paper
• coloc : Vignette, Paper

Recommended Readings/Videos

• Main reading on genome-wide association study design and post-GWAS in silico analysis
  • Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., & Lappalainen, T. (2021). Genome-wide association studies. Nature Reviews Methods Primers, 1(1), 1–21. https://doi.org/10.1038/s43586-021-00056-9
• Review of fine-mapping concepts and methods
  • Schaid D. J., Chen W., Larson N.B. (2018). From genome-wide associations to candidate causal variants by statistical fine-mapping. Nature Reviews Genetics.Link