Approved research

Lipid levels and risk of spontaneous intracerebral hemorrhage: a mendelian randomization study

Lay summary

Novel therapies are urgently needed for spontaneous intracerebral hemorrhage (ICH), as this disease is responsible for 50% of stroke-related mortality/disability and has no effective proven acute treatments. This unmet need in the field of cerebrovascular disease research is more pressing than ever, as the incidence of ICH continues to rise due to the aging population and the widespread use of antithrombotic therapies. Observational studies that enrolled thousands of ICH patients found that a link between history of high cholesterol and a decreased risk of ICH. While promising, these studies are limited by their observational design, that precludes the possibility of establishing whether these results are causative or associative. Population genetics provides powerful tools to overcome the causal inference limitations outlined above. Common mutations linked cholesterol levels can be used as instruments to evaluate the causal relationship between different lipid fractions and risk of ICH. We aim to (1) determine whether the aggregate burden of lipid-related genetic risk variants for total is associated with risk of spontaneous intracerebral hemorrhage; (2) determine whether associations identified in aim 1 are mediated by specific lipid fractions (LDL versus HDL versus triglycerides); and (3) utilize both genetic data and laboratory measurements on lipid levels to implement genomic analyses to estimate the causal effect of lipid levels on risk of ICH. Associations between lipid-related genetic risk variants and risk of intracerebral hemorrhage will provide crucial evidence supporting a causal link between lipids and intracerebral hemorrhage. This results will point to a novel pathophysiological pathway to be targeted by preventive and therapeutic strategies. This project will take 24 months,