Session 5: Rare variants

session overview

• What are rare variants?
• Challenges in rare variant analysis of WGS data
• Conventional rare variant tests
• New rare variant tests
• STAARpipeline: Functionally-Informed WGS Analysis Pipeline

Suggested Readings

• Byrska-Bishop, M., Evani, U. S., Zhao, X., Basile, A. O., Abel, H. J., Regier, A. A., Corvelo, A., Clarke, W. E., Musunuri, R., Nagulapalli, K., Fairley, S., Runnels, A., Winterkorn, L., Lowy, E., Human Genome Structural Variation Consortium, Paul Flicek, Germer, S., Brand, H., Hall, I. M., … Zody, M. C. (2022). High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios. Cell, 185(18), 3426–3440.e19. https://doi.org/10.1016/j.cell.2022.08.004
• Overview of rare variant association analysis: https://pubmed.ncbi.nlm.nih.gov/20479773/
• Rare variant analysis study design:
  • https://www.cell.com/ajhg/fulltext/S0002-9297(14)00271-7
  • https://www.nature.com/articles/s41576-019-0177-4
• Methods for rare variant association analysis:
• STAAR: https://www.nature.com/articles/s41588-020-0676-4
• Burden test: https://pubmed.ncbi.nlm.nih.gov/18691683/
• SKAT: https://pubmed.ncbi.nlm.nih.gov/20560208/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135811/
• ACAT-V: https://pubmed.ncbi.nlm.nih.gov/30849328/