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Approved research

Functional significance of noncoding human mutations

Principal Investigator: Dr Mark Gerstein
Approved Research ID: 41170
Approval date: December 7th 2018

Lay summary

Most disease-causing variants fall not in genes but in the spaces between them, about which much less is known. This presents a major challenge for interpreting most of the disease-associated single nucleotide polymorphisms (SNPs) identified in a project like the UK Biobank. We plan to leverage our expertise in noncoding regions and the UK Biobank genetic and phenotypic variation to devise a new, multi-dimensional scoring scheme for predicting the impact of individual SNPs. The health benefits are potentially very large because it could allow the scientific community to understand the significance of many more disease-associated SNPs. Because of the relatively unexplored nature of the vast noncoding genome, we have no clear end date for the project.

Scope extension:

How can we use the rich genotype-phenotype associations in the UK Biobank to better interpret the functional significance of noncoding human mutations to better understand health and disease?

Aim 1. Develop a new, comprehensive scoring scheme for the pathogenicity and functional significance of noncoding single nucleotide variants.

Aim 2. We plan to leverage the additional wearable and imaging data to generate risk scores for various phenotypes within UKBB. Additionally, by leveraging more precise phenotypes derived from these data, we can identify and prioritise genetic variants of interest.