Using established summary statistics from GWAS of phenotypes that relate to psychopathology and cognitive ability to calculate polygenic risk scores
Exaggerated reactivity of the amygdala, a deep brain structure critical for coordinating our responses to danger, has been documented in almost all common forms of mental illness. More importantly, exaggerated amygdala reactivity predicts who may experience mental illness in response to future stress. Thus, amygdala reactivity could be useful as a risk biomarker in evolving efforts to help prevent mental illness. However, direct measurement of amygdala reactivity using functional MRI is neither easy nor inexpensive. We propose to establish a genetic signature of threat-related amygdala reactivity to overcome this measurement limitation using easy and inexpensive collection of DNA.
In addition to the above, as we are also interested more broadly in the genetic correlates of cognitive and mental health, we will use established summary statistics from GWAS of phenotypes that relate to psychopathology and cognitive ability, to calculate polygenic risk scores in the UK biobank, and test whether they can predict psychiatric and cognitive phenotypes and/or their structural brain markers.
We also hope to look at cognitive ability, structural brain integrity, and health behaviors. We will use accelerometer and other health data (smoking, drinking, activity levels, weight) to test whether healthier lifestyles may predict both better cognitive ability and higher structural integrity in the brain as individuals age. SEM will be used to model the effects of aging on longitudinal changes in brain MRI to add an additional dimension to analyses.