When I began my MSc thesis last July, I was mostly driven by a frustration over the complexity of schizophrenia. So many genes, mutations, as well as environmental factors, and the etiology of the disease still remains unclear. I decided to make my small but still a contribution to this field by investigating DTNBP1, a gene long suspected to play a role in schizophrenia. Despite over two decades of research, its true impact is not well defined. I set out to re-examine this question using a meta-analysis of case-control studies and supplemented it with in silico tools to predict the functional effects of individual genetic variants in brain tissue.

My analysis revealed that while rs2056943 emerged as statistically significant in the meta-analysis, it lacked evidence for functional regulatory effects based on in silico predictions. In contrast, several SNPs demonstrated strong regulatory potential:

• rs74210
• rs3829893
• rs4236167
• rs1018381
• rs3213207

These SNPs were found to affect:

• Transcription factor binding
• Chromatin state
• Gene expression in key brain regions like the cortex and hippocampus

These variants may influence neuronal development or synaptic function in ways that are not captured by genome-wide association studies (GWAS), which often miss non-coding regulatory effects. Future studies might expand on these findings by validating functional effects in neuronal models or exploring their role in early neurodevelopment.

Ms. Uliana Andreeva (Student) MSc
SOLS MAHE Dubai