Meeting the Challenge of Systems Biology in Traumatic Brain Injury: Beginning Reverse Translation with Epigenome-Wide Association Studies

Excerpt

We live in an age of biological wonders. Advancement in the understanding of human disease has accelerated since the sequencing of the human genome in 2001, and the development of the science and methodology of genome-wide association studies (GWAs) [1]. Interest in the genetic underpinning of disease has been fueled by the early successes in the 1990s of eloquent linkage studies, which specifically identified highly penetrant single genes that cause Huntington’s disease, myotonic dystrophy, and the spinocerebellar ataxias. A key misinterpretation of the fundamentals of GWAs, primarily used to study complex diseases, is the idea that these association studies will identify single genes with high penetrance, which will be useful to infer causation and calculate risk. Most common, prevalent, complex diseases, such as diabetes and stroke, do not have single genes as risk factors. Conditions caused by trauma are different. Causation is never based on a genetic foundation. However, responses to injury can be associated with specific genes and gene networks, and the value of GWAs in these settings is that they can identify complex biological systems that influence responses to injury [2]. …