Large genetic study identified shared DNA between smoking, cannabis use, and schizophrenia | Research

The takeaway

A genome-wide analysis of over 780,000 people found a shared genetic factor explaining 8.6% of schizophrenia risk, with the gene NCAM1 emerging as a key link between smoking, cannabis use, and schizophrenia.

Genetics researchers, psychiatrists studying schizophrenia risk factors, and policymakers evaluating cannabis-psychosis evidence.

Shared genetic factor explained 8.6% of schizophrenia heritability

What the researchers found

A common genetic factor of cannabis and cigarette smoking explained 8.6% of schizophrenia heritability. Twenty independent loci were identified, with NCAM1 (neural cell adhesion molecule 1) highlighted as a top risk gene. Risk genes were enriched in cortex, neurons, and dendritic spines.

Why it matters

This study provides genetic evidence that the association between cannabis/smoking and schizophrenia is partly driven by shared biology, not just behavioral choices. NCAM1 is involved in neurodevelopment, suggesting a common vulnerability.

The numbers in context

Over 780,000 total participants. Shared genetic factor explained 8.6% of schizophrenia heritability. 20 independent genome-wide significant loci. Top variant rs7945073 on chromosome 11. Genetic correlations with ADHD (r=0.50), social deprivation (r=0.58), lifestyle problems (r=0.83).

How the study worked

Leveraged genome-wide summary statistics from three large datasets: schizophrenia (n=99,934), cigarette smoking (n=518,633), and cannabis usage (n=162,082). Applied CAUSE and Genomic SEM to identify shared genetic architecture.

What this study cannot tell us

Summary-level statistics cannot establish individual-level causation. The study population was primarily European ancestry. The 8.6% explained heritability leaves most of the shared risk unexplained.

How to read the evidence

Strong: very large combined sample (780,000+), rigorous genomic methods, multiple validation approaches.

When this study was published

Published in 2022.

The bigger picture

The debate over whether cannabis causes schizophrenia or whether shared genetics explain both is central to public health policy. This study supports the shared genetics model while not ruling out direct causal effects.

Questions still open

Does the shared genetic factor mean cannabis is less causally related to schizophrenia than assumed? Could NCAM1 variants identify individuals at highest risk? Do the remaining 91.4% of schizophrenia heritability factors interact with cannabis use?

Common questions

What is NCAM1?

NCAM1 (neural cell adhesion molecule 1) is a gene involved in brain development, specifically in how neurons connect and communicate. It was identified as the top risk gene shared between smoking, cannabis use, and schizophrenia.

Does this mean cannabis does not cause schizophrenia?

Not exactly. It means some of the association is explained by shared genetics, so people genetically predisposed to schizophrenia may also be predisposed to use cannabis. But this does not rule out that cannabis also has direct effects on psychosis risk.

What else was genetically correlated?

The shared genetic factor was also correlated with ADHD risk (r=0.50), social deprivation (r=0.58), lifestyle problems (r=0.83), and pregnancy loss (r=0.60).

Read the original research

Genome-wide identification of the shared genetic basis of cannabis and cigarette smoking and schizophrenia implicates NCAM1 and neuronal abnormality.

Psychiatry research, 310, 114453

View on PubMed ↗Publisher’s paper ↗

Citation

Song, Weichen; Lin, Guan Ning; Yu, Shunying; Zhao, Min. (2022). Genome-wide identification of the shared genetic basis of cannabis and cigarette smoking and schizophrenia implicates NCAM1 and neuronal abnormality.. Psychiatry research, 310, 114453. https://doi.org/10.1016/j.psychres.2022.114453