Rare variants contribute to development of familial cancer.  Genes carrying rare variants may contribute to molecular mechanisms of sporadic cancers.  Historically, many of the rare variants were discovered by co-segregation with the disease in cancer families.  However, recent progress in population scale sequencing opens new opportunities for using association analysis for detection of rare variants.  

The standard methods of association analysis were developed for common variants.  While the standard regression framework and population stratification approaches hold in the rare-variant analysis, it may additionally require (i) aggregating of variants per gene (or pathway), (ii) weighting by biological significance and allelic frequency, and (iii) applying permutation-style tests for estimating statistical significance.  

The webinar will discuss these features of rare-variant analysis and illustrate their implementation using SKAT R library.