Genetics of Chronic Traumatic Encephalopathy

All neuropathologically confirmed chronic traumatic encephalopathy (CTE) cases in the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank had prior exposure to repetitive head impacts (RHI), although not all individuals exposed to RHI had CTE, suggesting that genetic risk factors may also contribute to CTE risk. Identification of genes that increase the risk of CTE may help us understand the etiology and biological mechanisms behind the disease. Genetic risk factors may also be used to aid in counseling contact sport athletes of their risk of developing CTE and may provide targets for disease-modifying drugs for CTE. In this chapter, we explore methodological approaches to studying the genetics of CTE, including appropriately choosing control subjects, using endophenotypes, and modeling gene-RHI interactions. We also explore candidate genes for CTE, including APOE and MAPT . Lastly, we discuss ethical considerations for genetic testing in the clinic for youths planning to engage in contact sports. The study of CTE genetics is nascent, but future discoveries could greatly affect care of patients with CTE.