The role of interferons in the risk of cerebrovascular disease

Stroke and dementia are leading causes of mortality and disability worldwide. People who survive a stroke have a higher risk of suffering from a second stroke or developing dementia despite best available treatments. Persistent inflammation in the blood may account for this residual risk of stroke and represents a promising treatment target for stroke. Interferons are inflammatory substances released in the bloodstream by white blood cells to fight viruses. Diseases caused by an abnormally high release of interferons in the circulation are observed with genetic mutations in key regulators of this release. These genetic diseases of interferons have manifestations that resemble those encountered in people with stroke in the general population, such as brain vessel damage. Such genetic disease, however, are uncommon. The aim of our project is to determine whether people who have smaller variations in the genes that cause diseases of interferon (called single nucleotide variants), usually thought to be harmless, have an increased risk of stroke. We will use data from the UK Biobank to identify people with small variations in these genes and compare their risk of stroke, dementia and other conditions observed in genetic diseases of interferons with people that do not carry such variations. Our results may help identify interferons as a potential cause of stroke and pave the way to studies aiming to prevent stroke by targeting this inflammatory substance.