Approved Research

Fine mapping copy number variants for behavioral traits

Lay summary

Sometimes, errors in DNA copying result in deletions or duplications of entire sets of genes. It has been observed that for some of these gene sets (called copy number variants, CNVs), people who carry deletions or duplications show an increased risk for behavioral disorders, such as autism, schizophrenia, obesity, bipolar disorder, and intellectual disability. Since many genes are deleted or duplicated within each CNV region, in order to treat these behavioral disorders, we will want to know which gene(s) within each CNV are driving which disorder. To answer this question, we will study how the increase or reduction of RNA copies (as a result of DNA duplications or deletions, respectively) affects risk for each trait. Because the number of RNA copies for each gene varies between all individuals, we will be able to utilize information from large groups of people who don't have CNVs in order to tell us something about the people who do.

Over the next two years, we will apply computational methods to UK Biobank individuals, in order to detect genes within the CNV regions that have RNA levels that are associated with disease. Besides identifying individual genes contributing to disease, we also hope to identify networks containing CNV genes that are contributing to disease, as well as any groups of genes within each CNV that work together to cause disease. The result of the study will enable the design of targeted therapies for people who have CNVs and behavioral disorders. Furthermore, because the data we use is coming from the general population, any genes that we map to behavioral disorders in our study of CNVs will also be risk factors for the disorders in everyone else.