Clinical and Molecular Outcomes of Genomic Signatures in Autism

Autism is a neurodevelopmental condition diagnosed in 1-2% of children.

Hundreds of genes have been implicated in autism, but a relatively low percentage of autistic individuals have an identifiable single-gene cause for their condition. A combination of other genetic information, such as polygenic risk scores (PRS), is not used in clinical settings yet.

Additional investigations are needed to improve the use of genetic information, such as using biological information to improve the genetics scores. Limited information on the effects of high PRS on molecular and cellular phenotypes in neural development.

Here, we aim to estimate better how to use biological information such as gene ontology to calculate genetic risk scores from both common and rare variants in autism.

We specifically hypothesize that these genetic scores calculated for genes encoding for RNA regulators are associated with co-occurring conditions and severity.

Furthermore, we will obtain the multi-omic profiles of neural cells and cerebral organoids generated from induced pluripotent stem cells of carriers with high common RNA regulator PRS and compare these with already available single-gene cellular models. Lastly, we will use genomic and molecular data to identify putative drug targets for subgroups in ASD.

Our project will hopefully lead to a better understanding of autism at the genetic and molecular level and improve the use of the data in clinical settings.