| Title: | Genetic analyses of dyslipidemia in cardiometabolic disease: Integrating genomics, metabolomics, and drug-target insights from the UK Biobank |
| Lead Institution: | Umea University |
| Principal investigator: |
Application 148828
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About
Heart disease and stroke are often caused by a disease called atherosclerosis. The disease is characterized by the hardening and narrowing of the arteries. The narrowed arteries have an increased risk of blood clot formation. The most common localizations of atherosclerosis are the heart and the brain. Here, the blood clots can cause heart attacks or strokes. Chronic narrowing of the arteries without blood clots can also cause exercise-related chest pain (angina), arrhythmia, and structural heart disease, leading to heart failure. A major cause of atherosclerosis is elevated levels of blood fat and cholesterol particles in the blood. When blood fats and cholesterol are elevated, excess is deposited in the arterial wall. Here, the deposited fat and cholesterol degrade, which causes inflammation and scar formation. Other common factors that cause atherosclerosis are high blood pressure, diabetes, and smoking. People who fall ill due to heart disease or stroke, or have a high risk of these diseases, are often recommended preventive measures. These can be lifestyle-based interventions such as entering a smoking cessation program. If the blood pressure is elevated, it can involve taking a medication such as blood pressure lowering. Another important intervention can be taking statins to lower the circulating levels of blood fats and cholesterol. However, some people do not reach the treatment target of lowered blood fats and cholesterol despite taking their medications and changing their lifestyles. This can be due to drug intolerance, hereditary genetic disease that causes severely elevated levels of blood fats and cholesterol, or other reasons. Several bodily processes affect the circulating levels of blood fats and cholesterol. Available therapies modify some of them. We want to find out if other processes can be modulated to lower blood fat and cholesterol particles safely and if that would help to lower the risk of heart disease and stroke in individuals who need it. We can help in answering these questions by analyzing the vast genetic, metabolic, and health-outcome-related data available in the UK biobank. This means that the UK Biobank's wealth of data can help find out which genes can be safely and successfully targeted by future medicines to prevent atherosclerosis. In summary, our research aims to find better treatments that can help prevent atherosclerotic disease and reduce heart attacks and strokes. The planned analyses will be performed within the 36-month period. This proposal does not involve the re-contact of participants.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 12175 | Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk | Fredrik Landfors (+4) | 2024 | European Heart Journal Open |
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