Largest Genetic Study of Cannabis Use Found Four Genes and a Strong Genetic Overlap With Tobacco | Research

The takeaway

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.

Read this if you are interested in whether there is a genetic component to cannabis use.

83% genetic correlation between lifetime cannabis use and cigarette smoking.

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Strong evidence from the largest genome-wide association study of cannabis use to date, with replication samples and rigorous statistical methods.

When this study was published

Published in 2016. Subsequent GWAS studies with even larger samples have confirmed and extended these findings.

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.

Questions still open

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?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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