Tope Agabalogun

Schizophrenia and autism are complex psychiatric disorders that affect approximately 1.1% of US adults and 1.4% of US children. Though much is still unknown about the etiology of these disorders, genomic analysis has provided some insights into the genetic underpinnings of these neuropsychiatric disorders. Recent studies have suggested that missense and loss-of-function (LOF) de novo (i.e. newly arising) mutations in the FMRP-I gene set may be implicated in the development of schizophrenia and autism. A current point of contention is the nature of the enrichment of de novo mutations of genes that interact with FMRP. This enrichment might suggest that FMRP acts in a mechanistically causal manner as risk to schizophrenia and autism. Alternately, this enrichment might simply be a proxy for other attributes of a set of genes identified to interact with FMRP, such as gene size or neuronal expression. In an attempt to more precisely evaluate the nature of this enrichment, we performed gene set enrichment analysis (GSEA) to examine the relative level of LOF mutations in the FMRP-I gene set compared to other neuronally expressed genes that were curated from RNA sequencing data. When brain expression was accounted for, the FMRP signal for de novo enrichment attenuated, but persisted overall, suggesting that brain expression may play some role in accounting for the enrichment in de novo LOF mutations within this gene set. Further analysis may provide insights into understanding the role that the FMRP-I gene set may play in the development of schizophrenia and autism, and potentially suggest avenues for subsequent studies that may shed light on some of the causal pathways in these disorders.

 

PROJECT: FMRP-I and neuronal enrichment in psychiatric disorders

Mentors: Daniel Howrigan and Ben Neale, Stanley Center for Psychiatric Research
 

 

Tope Agabalogun

My summer at the Broad was a transformative experience that pushed the boundaries of how I think about diseases and the daunting challenges of addressing them. I was mentored, encouraged, and challenged within this community, and SRPG provided a great atmosphere to grow personally and as a scientist. Through SRPG, I honed my ability to think critically about scientific problems and discuss the nuances of my research with a wider audience. Above all, I was fortunate to join a community driven by an explicit mission to work collaboratively to translate scientific insights into clinical advances for patients.