REPRODUCIBLE FUNCTIONAL CONNECTIVITY ENDOPHENOTYPE CONFERS HIGH AUTISM RISK IN SUBSET OF INDIVIDUALS

Functional connectivity (FC) analyses of individuals with autism spectrum disorder (ASD) have established robust alterations at the group level. Yet, the translation of these imaging findings into robust markers of individual risk is hampered by the extensive heterogeneity among ASD individuals. Here, we report an FC endophenotype that confers a greater than 7-fold risk increase of ASD diagnosis in the general population. By focusing on a subset of individuals with highly predictive FC alterations, we achieved a greater than 3-fold increase in risk over previous predictive models. The FC risk endophenotype was characterized by underconnectivity of transmodal brain networks and generalized to independent data. Our results demonstrate the ability of a highly targeted prediction model to meaningfully decompose part of the heterogeneity of the autism spectrum. The identified FC signature may help better delineate the multitude of etiological pathways and behavioural symptoms that challenge our understanding of the autism spectrum.