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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