Research question!(1) Resolving temporality and causality in the circulatory-brain axis. (2) Uncovering actionable circulatory biomarkers/factors for brain disorders early detection/intervention. (3) Providing a framework for targeting vascular health to mitigate neuropsychiatric burdens.
Objectives: (1) Establish Causality: Using Cox proportional hazards survival regression analysis, we will assess whether cardiovascular conditions temporally increase the risk of subsequent brain neuropsychiatric disorders. We will also use genome/environment factors as instrumental variables (e.g., Mendelian Randomization) to test the causality between these two types of diseases. (2) Identify shared genetic/environment risk factors: By integrating genomic data and environmental exposure records available in UKB, we aimed to identify common risk factors that jointly predispose individuals to both circulatory and neuropsychiatric conditions. (3) Reveal Potential Biological Pathways: By synthesizing genetic/environmental, proteomic, biochemical, imaging, clinical, and psychometric data, we aim to map out the biological pathways that bridge circulatory dysfunction and neuropsychiatric disorders. (4) Develop Predictive AI Models: One of the ultimate goals is to extract vascular biomarkers from the identified causal pathways, and further use them to construct artificial intelligence (AI) models to predict the onset, progression, and prognosis of neuropsychiatric disorders.
Scientific rationale for the research!Emerging evidence suggests complex interconnections between circulatory disorders and neurocognitive/mental health conditions. While clinical observations indicate higher rates of neuropsychiatric disorders (such as dementia and depression) among patients with circulatory disorders (hypertension, ischemic heart disease, and atherosclerosis, etc), the causal mechanisms between them remain unclear.
