Principal Investigator: Professor Erik Ingelsson
Department: Department of Medical Sciences
Uppsala University, Department of Medical Sciences, UCR/MTC, Dag
Hammarskjölds väg 14B, Uppsala 75237, Sweden
Lead Collaborators: Professor Michel Dumontier
Collaborating Institution Address:
Stanford University, Medicine, 1265 Welch Rd, Palo Alto CA 94305, United
States of America
1a: Cardiovascular disease, including heart disease and stroke, is the global
leading cause of morbidity and mortality. Recent advances in human genetics
open up new avenues for investigation of downstream effects of perturbation of
drug targets. By investigating the phenome-wide characteristics of individuals
carrying gene-disrupting alleles, we can characterize the phenotypic effects as a
function of the number of functional alleles of specific genes. Using this human
knockout model, we can simulate and predict what the result would be if
blocking the corresponding protein.
1b: Knowledge about associations of novel and known drug targets with
cardiovascular outcomes as well as with other phenotypes will give important
insights that can accelerate development of new treatment strategies. Hence,
the proposed research does meet UK Biobank’s stated purpose via improving the
prevention and treatment of chronic disease.
1c: Specific Aim 1: To predict potential for repurposing or cardiovascular side
effects of known drug targets using genetic information
We will perform single variant analyses, as well as burden tests (combining all
protein-disrupting variants within a gene), for all genes encoding known drugs
targets in relation to cardiovascular outcomes, as well as with common
cardiovascular side effects.
Specific Aim 2: To predict phenome-wide effects of drugs developed against
We will perform association analyses of drugs currently or previously in
development for treatment of cardiovascular disease with the whole range of
phenotypes available in the UK Biobank.
1d: Full cohort