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Genetics and Molecular Mechanisms of Impulse Control

  • Date: 2023-2027
  • Project leader: Roy Siddharth
Impulsivity influences decision making and impacts behaviours such as addictions, mal-adaptive internet use, educational achievement and criminal activity. Lack of impulse control can manifest as clinical disorders such as kleptomania, pyromania, intermittent explosive disorder, etc. This makes the study of its genetics and molecular mechanisms important. Previous GWASs have identified SNPs correlated with the trait, however the pathways influenced by such traits giving rise to the phenotype remains poorly understood. I am performing a multivariate GWAS using Genomic Structural Equation Modelling on some human impulsive phenotypes using unexplored genomic data from the UKbiobank. Subsquently, I shall perform a Transcriptome Wide Association Study (TWAS) and use the results with brain eQTL summary statistics to infer the differentially expressed genes from impulsivity. The human differentially expressed genes shall be combined with RNASeq data from impulsive zebrafish lines to determine the genes influencing impulsive behaviour which are evolutionarily conserved across species. Identified genes will be edited using CRISPR-Cas9 in zebrafish and their behaviour and cell biology shall be examined to determine the pathways being controlled by the genes. In colaboration with Dr. Maxim Freydin