Statistical methods for analyzing rare variants in next generation sequencing association studies

An increasing number of large scale sequencing association studies, such as the whole exome sequencing studies, have been conducted to identify rare genetic variants associated with disease phenotypes. Testing for rare variant effects in sequencing association studies presents substantial challenges. We first provide an overview of statistical methods for testing for rare variant effects in case-control and cohort studies, and then discuss statistical methods for meta analysis of rare variant effects in sequencing association studies and family sequencing association studies. The proposed methods are evaluated using simulation studies and illustrated using data examples.