Largest Genetic Study of Cannabis Use Found Four Genes and a Strong Genetic Overlap With Tobacco
In the largest genome-wide association study of cannabis use to date (32,330 people), researchers identified four genes linked to cannabis use and found an 83% genetic correlation between cannabis and cigarette use.
Quick Facts
What This Study Found
The International Cannabis Consortium pooled genetic data from 13 cohorts totaling 32,330 participants. While no single genetic variant reached genome-wide significance on its own, gene-based analysis identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC, and KCNT2.
NCAM1 had previously been linked to cigarette smoking and other substance use. CADM2 had been associated with body mass index, processing speed, and autism spectrum disorders, phenotypes also connected to cannabis use.
Across all common genetic variants combined, genetics explained 13-20% of the variation in lifetime cannabis use. The most striking finding was an exceptionally strong genetic correlation of 0.83 between lifetime cannabis use and lifetime cigarette smoking, meaning the genetic factors that predispose people to try cannabis are largely the same ones that predispose them to try cigarettes.
Key Numbers
32,330 participants in primary analysis. 5,627 in replication. Four genes identified: NCAM1, CADM2, SCOC, KCNT2. SNP heritability: 13-20%. Genetic correlation with cigarette smoking: r = 0.83 (p = 1.85 x 10^-8).
How They Did This
Meta-analysis of genome-wide association data from 13 cohorts (N=32,330) with four replication samples (N=5,627). Gene-based testing was performed using VEGAS. SNP-based heritability was estimated, and genetic correlations with cigarette use were calculated using LD score regression.
Why This Research Matters
This study establishes that cannabis use has a substantial genetic component (13-20% from common variants alone, with twin studies showing 40-48% heritability). The 83% genetic correlation with cigarette smoking suggests that shared genetic pathways drive substance initiation broadly, rather than cannabis and tobacco having separate genetic architectures.
The Bigger Picture
The high genetic correlation between cannabis and tobacco use challenges the idea that different drugs have unique genetic risk factors. Instead, there may be a shared genetic architecture for substance initiation that manifests differently depending on environmental availability, social context, and cultural norms. The identified genes point to neural cell adhesion and potassium channel pathways.
What This Study Doesn't Tell Us
No individual SNPs reached genome-wide significance, reflecting the polygenic nature of cannabis use. The study measured lifetime use (ever vs never), which lumps together experimental users and heavy chronic users. Different genetic factors may influence initiation versus progression to problematic use. Most participants were of European ancestry, limiting generalizability.
Questions This Raises
- ?Are the genetic factors for cannabis initiation different from those for cannabis dependence?
- ?Would larger sample sizes reveal additional genes?
- ?Do the identified genes affect the subjective experience of cannabis, or do they influence general risk-taking behavior?
- ?Could genetic risk scores eventually predict vulnerability to cannabis use disorder?
Trust & Context
- Key Stat:
- 83% genetic correlation between lifetime cannabis use and cigarette smoking.
- Evidence Grade:
- Strong evidence from the largest genome-wide association study of cannabis use to date, with replication samples and rigorous statistical methods.
- Study Age:
- Published in 2016. Subsequent GWAS studies with even larger samples have confirmed and extended these findings.
- Original Title:
- Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.
- Published In:
- Translational psychiatry, 6(3), e769 (2016)
- Authors:
- Stringer, S, Minică, C C, Verweij, K J H(2), Mbarek, H, Bernard, M, Derringer, J, van Eijk, K R, Isen, J D, Loukola, A, Maciejewski, D F, Mihailov, E, van der Most, P J, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, J J, Abdellaoui, A, Bigdeli, T B, Branje, S J T, Brown, S A, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, S D, Harris, J M, Hartman, C A, Henders, A K, Heath, A C, Hickie, I B, Hickman, M, Hopfer, C J, Hottenga, J J, Huizink, A C, Irons, D E, Kahn, R S, Korhonen, T, Kranzler, H R, Krauter, K, van Lier, P A C, Lubke, G H, Madden, P A F, Mägi, R, McGue, M K, Medland, S E, Meeus, W H J, Miller, M B, Montgomery, G W, Nivard, M G, Nolte, I M, Oldehinkel, A J, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, J A, Richarte, V, Rose, R J, Shin, J, Stallings, M C, Stiby, A I, Wall, T L, Wright, M J, Koot, H M, Paus, T, Hewitt, J K, Ribasés, M, Kaprio, J, Boks, M P, Snieder, H, Spector, T, Munafò, M R, Metspalu, A, Gelernter, J, Boomsma, D I, Iacono, W G, Martin, N G, Gillespie, N A, Derks, E M, Vink, J M
- Database ID:
- RTHC-01275
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Is cannabis use genetic?
Partially. This study found that common genetic variants explain 13-20% of variation in lifetime cannabis use, and twin studies suggest 40-48% heritability overall. Four specific genes were identified, but hundreds of genetic variants likely contribute small effects.
Are the same genes involved in cannabis and tobacco use?
Largely yes. This study found an 83% genetic correlation between cannabis and cigarette use, meaning the genetic predispositions are highly overlapping. This suggests a shared biology of substance initiation rather than drug-specific genetics.
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Cite This Study
https://rethinkthc.com/research/RTHC-01275APA
Stringer, S; Minică, C C; Verweij, K J H; Mbarek, H; Bernard, M; Derringer, J; van Eijk, K R; Isen, J D; Loukola, A; Maciejewski, D F; Mihailov, E; van der Most, P J; Sánchez-Mora, C; Roos, L; Sherva, R; Walters, R; Ware, J J; Abdellaoui, A; Bigdeli, T B; Branje, S J T; Brown, S A; Bruinenberg, M; Casas, M; Esko, T; Garcia-Martinez, I; Gordon, S D; Harris, J M; Hartman, C A; Henders, A K; Heath, A C; Hickie, I B; Hickman, M; Hopfer, C J; Hottenga, J J; Huizink, A C; Irons, D E; Kahn, R S; Korhonen, T; Kranzler, H R; Krauter, K; van Lier, P A C; Lubke, G H; Madden, P A F; Mägi, R; McGue, M K; Medland, S E; Meeus, W H J; Miller, M B; Montgomery, G W; Nivard, M G; Nolte, I M; Oldehinkel, A J; Pausova, Z; Qaiser, B; Quaye, L; Ramos-Quiroga, J A; Richarte, V; Rose, R J; Shin, J; Stallings, M C; Stiby, A I; Wall, T L; Wright, M J; Koot, H M; Paus, T; Hewitt, J K; Ribasés, M; Kaprio, J; Boks, M P; Snieder, H; Spector, T; Munafò, M R; Metspalu, A; Gelernter, J; Boomsma, D I; Iacono, W G; Martin, N G; Gillespie, N A; Derks, E M; Vink, J M. (2016). Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.. Translational psychiatry, 6(3), e769. https://doi.org/10.1038/tp.2016.36
MLA
Stringer, S, et al. "Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.." Translational psychiatry, 2016. https://doi.org/10.1038/tp.2016.36
RethinkTHC
RethinkTHC Research Database. "Genome-wide association study of lifetime cannabis use based..." RTHC-01275. Retrieved from https://rethinkthc.com/research/stringer-2016-genomewide-association-study-of
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.