Project Summary/Abstract Inflammatory bowel diseases (IBD) are a group of chronic, debilitating disorders of the gastrointestinal tract with peak onset in adolescence and early adulthood. More than 1.4 million people are affected in the USA, with an estimated direct healthcare cost of $6.3 billion per year. The pathogenesis of IBD is not clear but previous studies have found IBD highly heritable. Therefore, studying the genetic basis of IBD is a natural path towards elucidating the IBD pathogenesis and will ignite the much-needed progress toward novel IBD therapeutics. Genome-wide association studies (GWAS) have identified over 200 loci associated with IBD. However, most IBD-causing low frequency and rare variants have yet to be discovered as GWAS only captures common variants. Sequencing studies can capture rare and low frequency variants but there has not been a well powered study yet. This study proposes an exome-wide association analysis on the recently generated IBD data from CCDG, a new and better powered dataset, with the goal to identify novel IBD genetic associations driven by low frequency coding variants. Results from this study will be promptly released and contributed to other IBD genetics studies. The new IBD causal variants, biological pathways and genetic mechanisms from this study will provide new insights into IBD pathogenesis, make important positive impact and serve as the fundamental resource and basis toward novel IBD therapeutics.