A genome-wide scan of families with high addiction rates found overlapping chromosomal regions linked to both alcohol and cannabis dependence, particularly on chromosomes 2 and 10.
Read this if you're curious about the genetic basis of addiction and whether alcoholism and cannabis dependence share genetic roots.
Chromosomes 2 and 10 showed overlapping linkage signals for alcohol and drug dependence
What the researchers found
Using large multi-generational families from the COGA study, researchers scanned the genome for regions linked to substance dependence using 1,717 genetic markers.
For alcohol dependence, significant linkage signals appeared on chromosomes 1, 2, and 10 (highest LOD score 3.7 on chromosome 10). For cannabis dependence, a notable signal appeared on chromosome 14 (LOD 1.9). For any illicit drug dependence, signals appeared on chromosomes 10 and 13.
When alcohol and drug dependence scores were combined, the strongest signals were on chromosomes 2 (LOD 3.2) and 10 (LOD 2.4 and 2.6 at different locations). The overlap on chromosome 10 for both alcohol-specific and broader substance dependence phenotypes suggested this region may harbor genes influencing general addiction vulnerability rather than substance-specific risk.
Why it matters
Identifying chromosomal regions linked to substance dependence is a step toward finding specific genes that influence addiction risk. The overlap between alcohol and drug dependence signals supports the idea that some genetic factors create a general vulnerability to addiction rather than risk for specific substances.
The numbers in context
Alcohol dependence: LOD 3.7 on chr 10 (60 cM), 3.4 on chr 2 (234 cM). Cannabis dependence: LOD 1.9 on chr 14 (95 cM). Any drug dependence: LOD 2.4 on chr 13 (64 cM). Combined: LOD 3.2 on chr 2, LOD 2.6 on chr 10.
How the study worked
Quantitative genome-wide linkage analysis using 1,717 SNP markers in large families from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-IV criteria counts for alcohol dependence, cannabis dependence, and any illicit drug dependence were analyzed individually and in combination.
What this study cannot tell us
Linkage analysis identifies broad chromosomal regions containing many genes, not specific causal variants. The COGA families were selected for high alcoholism rates, which may limit generalizability. LOD scores for cannabis dependence specifically did not reach genome-wide significance.
How to read the evidence
This is a well-powered genome-wide linkage study using well-characterized families, providing moderate evidence for genetic regions of interest, though individual findings require replication.
When this study was published
Published in 2008. Genome-wide association studies (GWAS) with much larger samples have since identified specific genetic variants for substance use disorders.
The bigger picture
This study contributed to the understanding that addiction has a significant genetic component and that some genetic risk factors are shared across substances. It helped guide subsequent gene-finding efforts that have identified specific addiction-related genes in these chromosomal regions.
Questions still open
- Which specific genes within these chromosomal regions drive addiction risk? Do the genes identified affect general reward processing, stress response, or other addiction-relevant pathways?
Common questions
Does this mean addiction is genetic?
What is a LOD score?
Read the original research
Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample.
Drug and alcohol dependence, 93(1-2), 12-20
Citation
Agrawal, Arpana; Hinrichs, Anthony L; Dunn, Gerald; Bertelsen, Sarah; Dick, Danielle M; Saccone, Scott F; Saccone, Nancy L; Grucza, Richard A; Wang, Jen C; Cloninger, C Robert; Edenberg, Howard J; Foroud, Tatiana; Hesselbrock, Victor; Kramer, John; Bucholz, Kathleen K; Kuperman, Samuel; Nurnberger, John I; Porjesz, Bernice; Schuckit, Marc A; Goate, Alison M; Bierut, Laura J. (2008). Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample.. Drug and alcohol dependence, 93(1-2), 12-20.
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