Cardiovascular diseases are the leading cause of death both worldwide and within the United States. These
diseases are heritable, however there is a large component of this heritability that remains unexplained with
current association studies. For example, a recent study on coronary artery disease (CAD) found that common
SNPs explained only half of CAD heritability. This “missing heritability” could be explained due to the current
focus on single nucleotide polymorphisms in the genetic architecture of cardiovascular diseases. I propose to
investigate the role copy number variants (CNVs) play in cardiovascular diseases.
First, I will develop novel sensitive methods to be able to detect smaller, and many more, CNVs within
individuals using genotype array data, one of the most widely available forms of genetic data. I will use this
method to call CNVs in one of the largest existing biobanks, UK Biobank. This will generate a large database
unique in the ability it provides researchers to detect associations between CNVs and cardiovascular diseases.
Second, using this large database, I will test for associations between CNVs and cardiovascular diseases,
likely leading to CNV-disease associations not previously known. Lastly, I will investigate the extent of CNV
burden among cases of heritable cardiovascular disease and how this burden is distributed across deletions
and duplications, and CNVs of varying spans and frequencies. Exploring and characterizing the role of CNVs
in cardiovascular diseases would further our knowledge of the biological mechanisms of these diseases and
could guide drug development and generate potential paths to preventing or treating these diseases.