Multimodal Approach to Endophenotype Discovery in Disorders with Genetic Liability

Abstract

Neurodevelopmental and Neurodegenerative disorders constitute a huge weight on society in terms of human suffering and economic cost. In recent years an increasing amount of emphasis has been placed on investigating the existence of endophenotypes of these disorders. An endophenotype is a measureable trait that lies between disease and underlying causes and can inform on the mechanistic understanding of behaviour, aid in the development of disease biomarkers and inform on the relationship between genes and behaviour. Investigating endophenotypes in monogenic disorders, which occur due to alterations in one gene such as the FMR1 gene and NRXN1 gene may help researchers to develop specific drug targets for these disorders. Moreover, some monogenic mutations can exhibit significant behavioural overlap with multifactorial disorders, such as in the case of FXS and ASDs or can be a contributing factor to a number of disorders such as NRXN1 deletions. The aims of this thesis was to utilise a multimodal approach to investigate the existence of cognitive, postural and electrophysiological endophenotypes in monogenic disorders in order to 1) Further characterise the phenotypic presentations of these disorders and 2) To utilise the knowledge gained to inform on overlapping disorders that are genetically more complex.