An Evolutionary Perspective on Human Cognitive and Behavioral Variation

Human cognition and behavior are highly heritable and so is liability to disorders that affect them. This includes neuropsychiatric disorders such as schizophrenia and autism spectrum disorder (ASD). We have been interested in understanding the genetic basis of susceptibility to ASD, as well as the more general relationship of genetic factors that influence human brain function to features of primate and human brain evolution. Since most disease associated variation impacts non-coding regions of the genome that are involved in gene regulation, we have focused heavily on understanding the regulation of gene expression and gene co-expression networks. Some of our studies suggest that derived, human-specific gene expression networks may preferentially impact human disease, especially risk for Alzheimer’s disease. More recently, we have started to integrate genetic risk data with the emerging maps of gene regulation to study human specific aspects of gene expression and gene regulation. These analyses indicate that human specific aspects of gene regulation, such as genes regulated by human specific enhancers, are indeed enriched in mutations or common genetic variants that increase risk for ASD and allied neurodevelopmental disorders. This provides evidence that genetic elements underlying human brain evolution are particularly susceptible to disruption in disease. Another aspect of work in this area indicates that disease risks are related to what are considered strengths in other areas, which leads us to a view of human brain function that emphasizes individual differences.