Prior research has shown that the immune system processes can influence risk of cognitive decline, but the exact mechanisms are not yet understood. Our hypothesis is that we can use genetics to better understand the relationship between the immune system and cognition. There is a set of immune-encoding genes (called HLA genes) that provide the instructions for the creation of immune-related proteins in the body. Another gene (called APOE) is known to influence cognition. Specifically, individuals who carry a certain version of this gene have a higher risk of developing dementia than individuals who do not carry that gene version, and the influence of this gene are stronger in women than in men.
Our research question is: Do immune-related HLA genes and versions of the dementia-associated APOE gene statistically interact with each other or with biological sex to influence lipid and cognitive outcomes? To answer this question, we will employ state-of-the-art computational and statistical genetics approaches in three large biobanks.
By identifying statistical interactions between HLA and APOE gene versions and/or with biological sex through this project, we will be able to better understand how genetic interactions with the immune system may lead to cognitive decline, and how these effects may differ in women and men.
