Deema Ali
Slide 1
Hi everyone, I’m Deema, a PhD student at the University of Galway. My research focuses on studying the role of FOXP1 transcription factor in schizophrenia risk and cognitive function across development.
Slide 2
Transcription factors are proteins that regulate gene expression by binding to specific regions of DNA.
They are crucial for controlling when, where, and how genes are turned on or off, influencing important processes including brain development.
One of the transcription factors we are interested in is Forkhead Box Protein P1, or FOXP1.
Which is expressed in both the developing and adult brain and is considered one of the key regulatory genes during neural development.
Rare mutations in this gene are associated with an autosomal dominant neurodevelopmental disorder known as FOXP1 syndrome, which is characterized by intellectual disability, developmental delay, and speech and language delays.
On the other hand, the recent schizophrenia-GWAS reported a number of genome-wide significant common variants within the FOXP1 gene.
In this study, we aimed to investigate whether FOXP1-regulated genes contribute to schizophrenia risk, and if this contribution varies across different developmental stages.
Slide 3
To investigate this, we analyzed transcriptomic data generated from mouse and human models of FOXP1 loss-of-function across different developmental stages, including prenatal and postnatal periods.
We used LD score regression analysis to determine whether FOXP1-regulated genes are enriched for schizophrenia heritability and we performed gene-set enrichment analysis to explore their overlap with schizophrenia-associated genes identified by single nuclei RNA-seq studies. We also studied the role of FOXP1-regulated genes in synaptic functions and how FOXP1-SNPs affect the expression of its downstream genes.
Slide 4
Our main findings show that FOXP1-regulated genes are enriched for SCZ heritability, and this enrichment is stage-dependent.
As we can see here that FOXP1-regulated genes show the highest enrichment for SCZ-associated genes during childhood and adolescence, while genes from the embryonic stage and newborn period show lower enrichment.
We’ve also found that the enrichment for genes associated with cognitive functions is similar to that seen in schizophrenia.
This highlights the importance of developmental timing in understanding genetic contributions to SCZ.
Thanks for your attention and I would be happy to discuss more details at my poster number 82
