Although increasing evidences have linked environmental exposures, such as air pollution, noise etc, to the risks of cardiovascular and cerebrovascular diseases, the underlying mechanisms remain unclear yet. Moreover, genetic susceptibility exerts effects on disease development during the whole life. Due to the great progress of Genome-Wide Association study on various phenotypes and diseases, many relevant single nucleotide polymorphisms (SNPs) have been identified. Recently, there are increasing interests to generate polygenic risk scores (PRS) by combining SNPs to reveal the accumulative effect of genetic variants on common diseases. To our knowledge, although some studies have paid attention to the interactions between environmental exposures, lifestyle and genetic susceptibility in the development of cardiovascular and cerebrovascular diseases, the underlying mechanism of interaction remain unknown. It is possible that genetic variants may modify the effects of environmental exposures on the risk of diseases.
Radiomics is a useful tool to study environmental exposures, and human health, because it potentially measures intermediate phenotypes that integrate exposures, genotype, and other host factors. It would allow efficient discovery of biomarkers and provide insight into molecular mechanisms of the interactions between environmental exposures, genetic susceptibility, and cardiovascular and cerebrovascular diseases. Furthermore, image genomics can combine medical imaging technology and genomics technology to explore the associations between lesion image features, genomic and molecular features and identify the macro-level image biomarkers used to predict the genome. Therefore, we propose to perform a prospective, comprehensive analysis by using the large-scale, high-quality data from UK biobank, which would help reveal the potential mechanisms of environmental exposures, and genetic variants on cardiovascular and cerebrovascular diseases.
In this study, we will construct PRS for SNPs that have been identified to be associated with cardiovascular and cerebrovascular diseases in GWAS and analyze the modified effects of genetic factors on the occurrence of cardiovascular and cerebrovascular diseases. Moreover, we will construct and compare new models and traditional models of cardiovascular and cerebrovascular diseases based on general and imaging data. Lastly, we will further explore the potential biological pathway and mechanism of cardiovascular and cerebrovascular diseases based on the imaging data and corresponding genetic data.
The results of the project can widen our knowledge on the interaction effects of environmental exposures, genetic factors in the development of cardiovascular and cerebrovascular diseases and provide insights into the biological mechanisms through which environmental exposures, lifestyle and genetic factors affect disease risk, improving targeted, early prevention of the diseases.
