Genome-wide search found no single gene strongly linked to starting cannabis use | Research

The takeaway

A genome-wide analysis of over 10,000 people found no individual genetic variants significantly associated with cannabis use initiation, suggesting many genes of very small effect are involved.

Read this if you are interested in whether there is a gene for cannabis use and why the genetics of behavior are so complex.

Only 6% of variation in cannabis initiation explained by common genes, despite 40% heritability

What the researchers found

Researchers conducted a meta-analysis of two genome-wide association studies (GWAS) involving more than 10,000 individuals to identify genetic variants associated with initiating cannabis use. No genetic variant reached genome-wide significance, and gene-based association testing also revealed no significant effects.

Using SNP-based heritability estimation, researchers calculated that only about 6% of the variation in cannabis initiation was attributable to common genetic variants. This is notable because twin studies have estimated the overall heritability of cannabis initiation at around 40%, suggesting that much of the genetic influence comes from rare variants, gene-gene interactions, or other sources not captured by common SNP arrays.

Why it matters

This null result is informative. It demonstrates that cannabis initiation is not driven by any single common genetic variant of large effect. The gap between the 6% SNP-heritability and 40% twin heritability suggests that the genetics of cannabis use initiation are highly complex and distributed across many genes.

The numbers in context

Over 10,000 individuals were included. No variants reached genome-wide significance. SNP-based heritability was approximately 6%, compared to twin study estimates of about 40% for overall heritability of cannabis initiation.

How the study worked

Meta-analysis of two genome-wide association studies with over 10,000 individuals. Standard GWAS methodology was used to test associations between common genetic variants and cannabis use initiation. Gene-based testing aggregated SNP effects within genes. SNP-based heritability was estimated using genomic-relatedness-based restricted maximum likelihood (GREML).

What this study cannot tell us

Sample size, while large for its time, may have been insufficient to detect variants of very small effect. Only common genetic variants were tested. Cannabis use initiation is a complex phenotype influenced by many non-genetic factors. The study focused on initiation, not progression to regular use or dependence.

How to read the evidence

Well-conducted GWAS meta-analysis, but the null result reflects the complexity of the phenotype and potential power limitations of the sample size.

When this study was published

Published in 2013. Much larger GWAS studies have since been conducted with hundreds of thousands of participants.

The bigger picture

This "missing heritability" pattern is common in behavioral genetics and addiction research. It suggests that future studies will need much larger sample sizes and potentially different methodological approaches (including whole-genome sequencing to capture rare variants) to identify the specific genetic architecture of cannabis use.

Questions still open

Would much larger GWAS studies (now routinely involving hundreds of thousands of participants) find significant associations? Are the genetic influences on cannabis initiation different from those on regular use or dependence? Where does the "missing" 34% of heritability reside?

Common questions

Is there a gene for cannabis use?

This study found no single gene strongly associated with starting cannabis use. The genetics appear to involve many genes of very small effect, with common variants explaining only about 6% of the total variation.

If cannabis use is 40% heritable, why did this study only find 6%?

The gap between twin study heritability (40%) and the 6% explained by common genetic variants is called "missing heritability." It likely reflects rare genetic variants, gene-gene interactions, and other genetic complexity not captured by standard genome scans.

Read the original research

The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation.

Addiction biology, 18(5), 846-50

View on PubMed ↗Publisher’s paper ↗

Citation

Verweij, Karin J H; Vinkhuyzen, Anna A E; Benyamin, Beben; Lynskey, Michael T; Quaye, Lydia; Agrawal, Arpana; Gordon, Scott D; Montgomery, Grant W; Madden, Pamela A F; Heath, Andrew C; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E. (2013). The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation.. Addiction biology, 18(5), 846-50. https://doi.org/10.1111/j.1369-1600.2012.00478.x