Functional Genetics and Psychiatric Disorders
An Exploration of Functional Genetic Variants in Candidate Genes for Psychiatric Disorders
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Drug addiction is a chronic disorder characterized by compulsive drug seeking and taking despite serious negative consequences. Association studies have identified a number of candidate genes harboring variants associated with susceptibility to addiction, but the causative variants frequently remain unknown. A solution to the challenge of identifying causative variants is the thorough characterization of functional genetic polymorphisms and their effects on regulation of candidate genes. I focused on candidate genes for drug addiction (ARRB2, DRD2, and DRD3) and made some novel and significant...
Drug addiction is a chronic disorder characterized by compulsive drug seeking and taking despite serious negative consequences. Association studies have identified a number of candidate genes harboring variants associated with susceptibility to addiction, but the causative variants frequently remain unknown. A solution to the challenge of identifying causative variants is the thorough characterization of functional genetic polymorphisms and their effects on regulation of candidate genes. I focused on candidate genes for drug addiction (ARRB2, DRD2, and DRD3) and made some novel and significant findings: The effects of two intronic SNPs in the human dopamine receptor D2 (DRD2) gene, previously shown to alter DRD2 alternative splicing, were confirmed in human brain autopsy tissues obtained from a population of cocaine abusers and controls. The same SNPs were significantly associated with cocaine abuse. The results of this study contribute to our understanding of the functional genetic variation in important candidate genes and have the potential to improve the prevention and treatment of drug addiction and other psychiatric disorders.
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