An analysis that compared the DNA of drug abusers with that of non-abusing controls has identified 89 genes that are likely to contain variants that contribute to addiction vulnerability.

Background: Vulnerability to addiction is a complex trait with strong genetic influences. Since the mid-1990s, scientists have been developing methods and tools to identify and evaluate the functional role of genes and their variants. The impact of such efforts has been greatly enhanced by the Human Genome and International HapMap Projects. By 2001, the first low-resolution genome-wide association studies from the NIDA-IRP’s Molecular Neurobiology Branch were published. Genetic research technology is now able to reliably scan the genome of individuals for genetic variants linked to specific functions.

Study Design: From 1990 to 2005, thousands of people participated in studies at NIDA-IRP’s Molecular Neurobiology Branch, providing self-reports and DSM Diagnostic Interview Schedule scores. From among this pool, researchers identified 980 African-American and European-American “drug abusers” (heavy lifetime use of illegal substances) and 740 controls (no significant history of addictive substances, no abuse, no dependence). Pooled DNA samples, prepared from blood extracted from each group were used to examine a panel of close to 640,000 genetic variations.

What They Found: Using strong statistical models that focused on the overlaps between the samples, this screen identified 89 genes that display clusters of genetic variants that are likely involved in addiction vulnerability. Most of these genes are expressed in the brain. Twenty-one of these genes influence cell adhesion, and nearly all of those are expressed in brain regions implicated in memory processes.

Comments from the Authors: The nature of the addiction-associated genes identified in this study, especially those involved in cell adhesion, suggest the critical role played by dysfunctional nerve cell connections in the addicted brain.

What’s Next: Other genes that emerged from the analysis are being tested in the context of where they are located in the brain and their likely functions: enzymes, transporters, receptors, protein processing, and transcriptional regulation. Results like these highlight characteristics that are common to human addiction and may facilitate efforts to develop targeted prevention and treatment strategies.

Source:The study, led by Drs. George Uhl and Qing-Rong Liu of the Molecular Neurobiology Branch at the National Institutes of Health Intramural Research Program at NIDA in Baltimore, was published in volume 141B, pages 1-8 (2006) of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).