Approved research

Genetic underpinnings of brain structural trajectories in health and psychiatric disease.

Lay summary

Rationale: It has been well-established that brain structure and cognition in psychiatric patients differ from control subjects at a group level. Additionally, it has been observed that brain plasticity and cognitive changes over time characterize the progression into disease better than a one-time point observation only. Twin and family studies have shown that at least part of the differences in brain structure can be attributed to genetic vulnerability for disease. This genetic vulnerability can also be assessed in a healthy population by computing (risk) scores for an individual based on their genotype. Aims: In this project, we aim to investigate the associations between the genetic predisposition for mental health, brain structure, and cognition in the UK biobank cohort. Additionally, we want to investigate whether the genetic predisposition for brain changes, or brain plasticity, is associated with outcomes such as mental health and cognition. When the data becomes available, we will associate the genetic predisposition for psychiatric disease and cognition with longitudinal brain changes in the UK biobank cohort. Project duration: The project will take approximately 1 year for aim 1), 1 year for aim 2), 2 years for aim 3) and 3 years for aim 4 (to allow for a longitudinal dataset that is as large as possible). Public health impact: This research will help understand the genetic underpinnings of changes in brain and cognition observed in healthy individuals and psychiatric patients. Both the polygenic risk score approach and brain age estimation based on machine learning techniques allow us to investigate at an individual level, irrespective of the presence of disease. With this research, we try to bridge the gap between group level analyses and personalized medicine. Identifying those at (genetic) risk may be a first step in that direction.