Thesis defense João Guimarães (Donders series 557)

19 September 2022

Promotors: Prof. dr. Christian F. Beckmann, Prof. dr. Barbara Franke
Co-promotors:: Dr. Emma Sprooten, Dr. Janita Bralten

Towards the shared genetic etiology of brain function, cognition and psychopathology
Human behavior is partly rooted in genes that influence brain systems whose function ultimately drive cognition, behavior and risk for psychiatric disorders. This implies that the domains of brain function, cognition and psychopathology are closely related to each other in their genetic influences. Yet, the three-way genetic relationship between brain, cognition and psychopathology have rarely been formally tested. In this thesis, we aimed to systematically and directly test three-way genetic relationship between brain function, cognitive traits and psychiatric disorders. We took advantage of recent big data resources and methodology to investigate (i) whether genetically correlated cognitive traits also exhibited overlap in their task-based brain activation by combining twin modeling and functional imaging meta-analysis, (ii) the presence and characteristics of general genetic factors underlying the amplitudes in the activation of multiple functional brain networks, (iii) whether the general factors of brain function were genetically correlated with previously reported general factors of cognition (g-factor) and psychopathology (p-factor). First, we showed, by looking at the genetic and neurobiological overlap between multiple cognitive functions, that fluid intelligence and cognitive flexibility converged in both their genetic and their neurobiological underpinnings. Then, by looking at the joint genetic architecture linking the function of many functional brain networks, we showed that their shared genetic influences can be efficiently represented by two distinct but correlated general factors, driven by the influence of many SNPs and genes. Further, we found that these two general genetic factors were not genetically correlated with the g- and p-factors. Altogether, the studies I describe in this thesis provide a framework for the study of the three-way genetic relationship between brain function, cognition and psychiatric disorders as well as crucial insight toward a better understanding of such relationship.