Team Shares 'Functionally Informed' Rare Variant Association Strategy

In PLOS Genetics, investigators with INSERM, the Institute of Translational Genomics in Germany, and other centers describe a rare variant association testing strategy that takes combined annotation dependent depletion (CADD) scores into account. The team's "rare variant association using functionally informed steps," or RAVA-FIRST, method looks at rare variant burdens across functionally informed CADD windows in whole-genome sequence data, the team explains. After using the approach to search for rare variant associations in simulated and real sequence data, the authors turned to RAVA-FIRST to find a rare variant-enriched region between chromosome 18 genes that was over-represented in individuals with early-onset forms of venous thromboembolism. "With RAVA-FIRST, we propose a novel strategy to investigate the role of rare variants in the whole genome that takes benefit from biological information," they write, noting that the strategy "relies on testing units that go beyond genes to gather rare variants in the association tests."