NIDA News Scan

Genome-wide association studies (GWAS), which scan the entire genome to find genetic variations (called SNPs) that are associated with particular diseases, have revolutionized the way scientists search for genetic causes of diseases, including drug and alcohol addiction. Most SNP research uses commercial microarrays, called ‘gene chips,’ which contain thousands of small pieces of DNA that recognize and bind to specific sequences of DNA in an experimental sample. Although a single gene chip can contain tens of thousands of small pieces of DNA, no chip can cover the entire human genome, and commercial chips tend to provide better coverage of some genomic regions than others. To test how well commercial microarrays include genes suspected to play a role in drug and alcohol addiction, researchers funded by NIDA first assembled a list of 910 genes known or suspected to be associated with addiction and found that commercial microarrays did not completely cover the possible SNPs found in these genes; for some genes, this lack of coverage was substantial. For example, a gene called CDH13, whose products activate a number of addiction-related signaling pathways in the brain, has 2,414 SNPs that are common in the African sample of the International HapMap project. However, only 50 percent of these SNPs were found on one of the commercial microarrays sampled. To supplement this incomplete coverage by commercial microarrays, the researchers developed a publicly available database for addiction researchers containing SNPs for the 910-gene set. All SNPs in the database are tagged with a prioritization score, which is intended as a measure of biological relevance to addiction. “Addiction researchers should find [the new database] to be a valuable tool, both in the design and interpretation stages of a GWAS,” conclude the authors.