Approved Research

Biomarkers, immunological signatures and hypertension-associated diseases - causal inference using genetic and observational approaches

Lay summary

Elevated blood pressure (BP) remains a major modifiable risk factor for mortality worldwide and leads to development of cardiovascular and cerebrovascular diseases. Variation in various BP indices possesses a widely recognized impact on target organs such as brain or heart. Therefore identification of pathways causally affecting BP that may be pharmacologically targeted is of major importance for public health.

In order to address the above question the current project aims to search for novel biomarkers and immunological signatures that causally affect the level of BP, and related cardiovascular traits such as vascular stiffness or coronary heart disease (CHD). This will be accomplished by using state-of the art methods from the field of epidemiology, and (population) genetics.

Advances in genomic research contributed to identification of major loci involved in pathogenesis of complex diseases such as asthma, hypertension, or CHD. A continuous increment of sample size of Genome Wide Association studies (GWAS) allows for constructing robust genetic risk scores and selection of Instrumental Variables (IVs) for Mendelian Randomization (MR) analyses, which can be further used to test causality between (intermediate) traits and diseases. For example, MR approach have provided evidence that genetically defined eosinophilia is causal for asthma development, while blood lymphocyte count may potentially causally affect development of hypertension and CHD. A similar approach can be applied to molecular biomarkers, such as blood level of proteins or metabolites and immunological signatures that may serve as exposure traits included in potentially causal pathways for traits of interest.

Using MR approach, current project aims to identify biomarkers and immunological signatures that are causal for the level of BP and related clinical traits. Additional observational (both cross-sectional and prospective) studies, linking biomarkers (e.g. OLINK-quantified plasma proteins, biochemical blood marker) or genetic variations to BP level and related cardiovascular traits, will be performed using data derived from the UK Biobank with data on various biomarkers and metabolites already available.

In summary, using state of the art genetic causal inference and epidemiological methods the current, 3-years project aims to identify and characterize molecular biomarkers and immunological signatures that may influence BP level and related traits in humans. Therefore it may contribute to a better understanding of hypertension pathophysiology and creating new treatment opportunities.