Approved research

Genetic determinants and biological pathways linking major inflammatory biomarkers to disease outcomes

Lay summary

Previous studies have identified genetic variation influencing inflammatory biomarker levels, but much of the genetic architecture remains unexplained. Also, previous analyses have questioned the causality of the associations between some inflammatory biomarkers and cardiovascular diseases whereas such studies for other disease outcomes are limited. Larger studies will be able to offer confirmatory answers. This application proposes to: (1) correlate genetic data with inflammatory biomarker levels to identify novel genetic determinants; (2) investigate associations between genetic polymorphisms related to inflammatory biomarkers, plasma levels of biomarkers and multiple disease outcomes related to inflammation; (3) examine causality of the associations This project will use the power, detailed phenotypic information, and prospective nature of UK Biobank to improve our understanding of the genetic determinants of major inflammatory biomarkers. Furthermore, it will examine which disease outcomes are likely to be causally related to chronic low-grade inflammation and empower the discovery of new drug targets informing medicines development for prevention of several chronic disease outcomes, thereby improving population health. Our analysis will involve correlating genetic changes found in the UKB participants with their blood levels of inflammatory biomarkers to identify important genetic factors. We will then explore the association between inflammation related SNPs identified through GWAS and multiple health outcomes. Finally, we will examine the interaction between environmental factors and genetic factors in relation to major disease outcomes associated with inflammation. These include cancer outcomes, cardiovascular outcomes and diabetes, infectious diseases, neurological outcomes, respiratory outcomes and skeletal outcomes. We will opt to use adjudicated outcomes, which will become available for the most common outcomes (i.e. cancer, cardiovascular outcomes and diabetes related outcomes) in 2015. For other outcomes we will decide whether we need to request access to hospital in-patient data and/or primary care data in order to fully ascertain our cases or wait until the adjudicated data are ready or to reply on HES data. We will also examine quantitative traits including BMI and waist circumference, lipid levels and glucose/HbA1c levels. The full cohort will be required.