Integration av -omik-metoder för identifiering av nya mål för läkemedelsbehandling och kliniska biomarkörer för koronarsjukdom
Tidsperiod: 2013-01-01 till 2015-12-31
Projektledare: Erik Ingelsson
Budget: 4 500 000 SEK
There is a large need for revitalization of the cardiovascular field with: a) improved risk stratification on the individual level through personalized medicine for more adequate individually-tailored treatments; and b) new targets for drug development based on pathways previously unknown to be involved in coronary heart disease (CHD) pathophysiology.The specific aims of this proposal include: a) Identification of causal genes and functional variants through re-sequencing and other fine-mapping methods in known CHD regions, combined with expression profiling in subcutaneous fat and skeletal muscle; b) Functional characterization of genes and pathways implicated in CHD pathophysiology via global metabolomic profiling, targeted proteomic profiling, and human system biology; c) Clinical biomarker identification and validation in the primary prevention setting.I will integrate genomic, transcriptomic, metabolomic and proteomic data from six longitudinal, population-based cohort studies (STHLM2, Karma, TWINGENE, PIVUS, ULSAM and GOSH) including >200,000 individuals; there are 2,368 incident CHD cases at time of submission, and the estimated number of cases by 2015 is 9,086.My work is anticipated to lead to new important insights of the pathophysiology of coronary heart disease, opening up new avenues for drug development, and leading to new biomarkers that will improve risk prediction and prognostication.