Genetic variants associated with PTSD and their impact on neuroimaging changes in the amygdala

• Grant number: 24/06731-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Jair de Jesus Mari
• Grantee: Davi Radamés Abrantes Fernandes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/12901-9 - National Center for Research and Innovation in Mental Health (CISM), AP.ESP

Abstract

Post-traumatic stress disorder (PTSD) is a complex disease that involves a set of symptoms developed due to a traumatic experience. In addition to similar symptoms, there are genetic correlations between major depressive disorder (MDD) and PTSD. Genome-wide association studies (GWAS) for the two disorders have identified variants associated with symptomatology and enriched for neural cells. A next step in post-GWAS analyses would be to check the individual action of these variants with other biological measures, such as neuroimaging approaches. The project's hypothesis is that the genetic variants found, when associated with neuroimaging changes in a Brazilian longitudinal cohort, may indicate differences in the volume of the amygdala. In addition, the known genetic correlation between PTSD and MDD raises the possibility of shared molecular pathways or structural changes. The project's objectives aim to correlate the variants or Single Nucleotide Variants (SNVs) between these disorders, understand the biological function of the involved genes, and observe the effects of the variants on the structure of the amygdala over 7 years of follow-up. The study will use data from individuals in the Brazilian High Risk Cohort Study (BHRCS). The most current PTSD and MDD GWASs will be used to select SNVs shared between these phenotypes, observing effect size and direction of the variants. Then, the genes of the selected SNVs with expression in the brain will be selected for functional annotation using tools like FUMA, MAGMA, and GTEx. Then, the genotyping and neuroimaging data of 362 probands from the BHRCS will be analyzed, relating the found variants to structural changes in the amygdala over 7 years. It is expected to find variants that share biological pathways, in addition to finding brain structural changes in the amygdala that may allow, in the future, the measurement of this and other structures to indicate risk and evolution of diseases.