Identifying novel high-impact rare disease-causing mutations, genes and pathways in inflammatory bowel disease patients

Our aim is finding the genetic causing of Inflammatory Bowel Diseases (IBD) from human rare variants which are carried by a very small portion of people in population. We are going to identify IBD causing variants, genes and pathways by using filtered high impact rare variants. Also, we plan to identify IBD genes by comparing IBD cases with healthy controls. Moreover, we will identify risk variants having comorbidity effects between IBD and other diseases, which is known that IBD patients have higher chance to be susceptible to some other disease, like Parkinson Disease. Finally, we are planning to conduct gene pathway analyses to rank the candidate IBD genes according to their importance from pathway and enrichment analyses.
It has been reported that rare variants may involve in pathogenesis of complex disease, aggregation of these rare variants could increase the chance of a combined unit (usually a gene) to be identified as a significant association for cases. We are going to use some state-of-art of method to perform IBD cases and controls studies to check which genes harbor more risk alleles in cases than controls. Besides, there are some well-established methods to filter high impact rare variants, which will increase more power in identifying disease related genes. We have sufficient calculation sources to finish this project. Calculations will be conducted on our local server (40 cores, 512 Gb RAM) or Mount Sinai Chimera clusters.
It will take 36 months to finish the project. The accomplishment of project will interpret which rare variants and their related genes contribute to inflammatory bowel disease. Moreover, filtered high impact variants could increase power of polygenetic risk score in classification, which is promising to be used in combining use with clinical factors in risk model to identify individuals at high risk of developing IBD. Lastly, we will provide a few new genes that are best candidates to be novel IBD-causing genes.