Approved Research

Phenome-wide association of human inherited structural variants in the UK Biobank

Lay summary

A major goal of genetic studies is to identify the genomic variants that contribute to human traits, including diseases. Current techniques can narrow down the disease-associated variants to small window(s) of the human genome. However, even within those small windows there are many different types of variants, and the precise variant that is responsible for the disease-association is unknown in most cases. The proposed project will focus on structural variants of the human genome, which lead to differences in large segments of our DNA sequences. Structural variants is relatively hard to identify at scale, in contrast to SNPs which only cause differences in a single nucleotide in our DNA. Our first aim is to develop methods to computationally infer the configuration of structural variants from the information provided by their neighboring SNPs. Using this method, we can infer the configuration of several large structural variants for each participant in the UKBB. We will then study the phenotypic associations of these structural variants using the large collection of phenotype data in UKBB. For each structural variant and its associated traits, we will also study the underlying mechanism by pinpointing the genes and/or proteins that mediate the association, using external functional genomic resources. Our project has the potential to discover disease-associated structural variants, provide insights into disease etiology and facilitate the development of new therapeutics.