Genome study unveils genetic ties between cannabis use disorder and lung cancer risk

In a recent study published in Nature Genetics, researchers conducted a genome-wide association study (GWAS) to gain novel insights into the pathophysiology of cannabis use disorder and public health concerns associated with the disorder.

Study: Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Image Credit: ShutterstockProfessional / Shutterstock.com Study: Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Image Credit: ShutterstockProfessional / Shutterstock.com

Background

Cannabis is a psychoactive drug with a long history of illegal use, mainly for recreational purposes. Chronic consumption of cannabis is associated with various health complications, including cognitive deficits, psychiatric disorders, and cancers.

Recently, many countries throughout the world have approved the use of cannabis for medicinal purposes and decriminalized its recreational use. In the United States, medical use of cannabis has been authorized in 37 states, whereas the recreational use of cannabis has been approved in 19 states. In Europe, Malta has fully legalized recreational cannabis.

With the recent changes in cannabis law, a gradual increase in the prevalence of cannabis use disorder has been observed worldwide.

The study

A GWAS meta-analysis of cannabis use disorder was conducted using the Million Veteran Program database, which is one of the largest biobanks in the world that complies with genetic, health, and lifestyle data to facilitate genetic research.

Additionally, a meta-analysis was conducted on data obtained from 1,054,365 individuals of European, African, mixed American, and East Asian ancestries designated by the reference panel used for assignment.  

Single nucleotide polymorphism (SNP)-based heritability was calculated within each ancestry using population-specific methods. 

Important observations

A total of 22 independent genome-wide significant (GWS) loci were identified within European ancestry, two GWS loci within African ancestry, one GWS locus within admixed American ancestry, and two GWS loci within East Asian ancestry.

The lead SNP for European ancestry was near the cholinergic receptor nicotinic alpha 2 subunit-encoding gene. For African ancestry, the lead SNP was in an intron of a gene that encodes for a pH-dependent proton-coupled amino acid transporter for glycine, alanine, and proline.

For admixed American ancestry, the lead SNP was in an intergenic region downstream of leucine-rich repeat-containing 3B. For East Asian ancestry, the lead SNP was intronic to the semaphorin 6D-encoding gene.  

Comparative analysis of cannabis use disorder and cannabis use traits with a range of psychiatric and nonpsychiatric traits showed a much more substantial overlap of cannabis use disorder with pathological and negative traits.

The calculation of SNP-based heritability within each ancestral group identified significant SNP-based heritability for three larger ancestries, including European, African, and mixed American ancestries.

The comparison of genetic correlations between cannabis use disorder and cannabis use revealed that the strongest positive correlations are related to smoking initiation and alcohol dependence. Comparatively, the strongest negative correlations are related to the age of first intercourse and smoking cessation.    

Further analysis identified a bidirectional causal relationship between cannabis use disorder and schizophrenia. Regarding the differences between cannabis use and cannabis use disorder, the analysis showed that cannabis use disorder is much more closely associated with psychopathology.

A unidirectional causal effect of multi-site chronic pain on cannabis use disorder was observed in the study. This indicates that chronic pain might act as a driving factor for cannabis use disorder.

The analysis further identified a unidirectional causal effect of cannabis use disorder on lung cancer. Conditional analysis of this result with smoking initiation did not significantly alter the relationship between cannabis use disorder and lung cancer. However, the conditional analysis with cigarettes each day mitigated this relationship.

A transcriptome-wide association study identified 36 and 15 genes using adult and fetal brain frontal cortex expression, respectively. DALR Anticodon Binding Domain Containing 3 (DALRD3) was the only common gene in these gene sets. Nonsense mutations in this gene are known to be associated with developmental delay and early-onset epileptic encephalopathy.

The observed gene associations included four distinct GWAS loci, including DALRD3 (both fetal and adult), ERCC8 (fetal), RP11-629G13.1 (adult), and PHLPP2 (adult). Proteins encoded by these genes are associated with various cancer types, including breast cancer, esophageal cancer, and multiple myeloma.

The estimation of SNP-based heritability of cannabis use disorder showed significant enrichments for the fetal brain frontal cortex but not for the adult brain cortex. This enriched fetal SNP-based heritability indicates that in the developing brain, genetic factors might play a role in inducing cannabis use disorder, even in the absence of cannabis exposure.    

Study significance

The study finds a significant difference between cannabis use and cannabis use disorder. Genetic liabilities to cannabis use disorder exhibit a much stronger association with psychopathology and disability. Notably, the study finds a causal link between cannabis use disorder and lung cancer risk.

Journal reference:
  • Levey, D. F., Galimberti, M., Deak, J. D., et al. (2023). Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics. doi:10.1038/s41588-023-01563-z.
Dr. Sanchari Sinha Dutta

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Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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Comments

  1. Darwin Trotter Darwin Trotter Costa Rica says:

    If this is meant to inform the general public, then it needs to be submitted in language the general public can understand. I learned.nothing from this post.

  2. Richard Matthew Jr Richard Matthew Jr United States says:

    The only people that get anxiety or schizophrenia feeling from marijuana or people that don't use it medicinally or as a regimen. If you smoke once in awhile, you're going to get anxiety and paranoia so to speak. If you use marijuana medicinally everyday, that feeling goes away a thousand percent. And for all these people that think all of a sudden their stories of marijuana and heart disease and lung cancer and all of this is coming from an experienced people that do not know how to phlush their products correctly and are in too much of a hurry to sell it and make money or smoke it to get high. That's why I am an ounce a week smoker and I am not for recreational marijuana whatsoever. If it comes down to that I will be forced to grow my own cuz you can't trust prescriptions these days and you can't trust people these days. But stopped casting all this negative stigma on the only thing that makes a lot of people happy. If it makes people happy and all of these faults that he's based on he said she said opinions, are redundant because if it makes somebody happy it makes them happy. If you feel schizophrenia and you get anxiety from it, then don't smoke it. just stopped talking about it already everybody's tired of hearing about it and the quality is going down hill as well because of all these people that are just uneducated and growing. That is the main problem. It does not cause cancer it does not do this and that like all your stupid stories say. What should be spoken up about more as people with no experience have no business in the Cannabis business

  3. Carol Smith Carol Smith United States says:

    I have smoked Marijuana since I was 21 years old. I am now 70 years old and am very very healthy. I am a chronic smoker. I do not smoke cigarettes or drink alcohol. I had polio and it has helped me deal with a lot of pain. I do not have any history of  any kind of mental illness. I eat healthy and do what amount of exercise I can do. I think how Marijuana effects people is how they take care of themselves and their mental strength. Just had to give my opinion.
    .

  4. Donald Henry Donald Henry United States says:

    This crowd resurfaces every time some new victory for free peoples in the cannabis sector is won. Now that Ohio has begun throwing off the yoke, enter a wave of propaganda like: known anticancer treatment is cancerous, known cognitive aid associated with cognitive deficits...this is ridiculous.

  5. Dbowl Dbowl United States says:

    That's why thca vapor is a safe smoke free and always has been a legal alternative to smoking weed. I'm from Georgia.

  6. Nunya Bizunes Nunya Bizunes United States says:

    Cannabis is a psychoactive drug with a recent history of illegal use, but a much longer history of human consumption reaching much further back than the biblical era, mainly for religious and/or medical purposes.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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