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Researchers link gene to cannabis abuse

June 18, 2019

New research from the Danish psychiatric project, iPSYCH, shows that a specific gene is associated with an increased risk of cannabis abuse. The gene is the source of a so-called nicotine receptor in the brain, and people with low amounts of this receptor have an increased risk of cannabis abuse.

Cannabis is the most commonly used illegal drug in both Denmark and internationally, and around one in ten users becomes addicted to the drug. Researchers from iPSYCH have discovered a gene that they associate with the abuse of cannabis.

"We discovered that the disorder was associated with a genetic variant. This variant affects how much of a certain nicotine receptor is formed in the brain," explains Associate Professor Ditte Demontis from Aarhus University, who is behind the study.

The genetic variant discovered by the researchers affects how much of a specific nicotine receptor is formed. People who have less of this receptor in the brain are at greater risk of becoming cannabis abusers.

Ditte Demontis and her colleagues used a nationwide Danish cohort to analyse the complete genome of more than 2,000 cannabis abusers and the genome of 50,000 control subjects. The researchers subsequently repeated these findings in an analysis of a further 5,500 cannabis abusers and more than 300,000 control subjects.

The researchers also included genetic data from studies in which researchers examined the underlying genetics for cognition such as e.g. the ability to complete an education.

Here, they found that people with a higher number of genetic variants associated with impaired cognition also have an increased risk of cannabis abuse.

"People who abuse cannabis often do worse in the education system, and our results show that this can be partly explained by genetics. That is to say that people with an abuse problem have more genetic variations in the genome which increase the risk of cannabis abuse, while at the same time negatively affecting their ability to get an education," explains Ditte Demontis.

The study is the first of its kind on this scale and represents a step towards understanding the particular biological mechanisms, which lie behind the abuse of cannabis.

"We need to undertake even more research into how the genetic differences in the genome contribute to the development of cannabis abuse, and we need to map out the precise biological mechanisms that lead to one person having a higher risk of becoming a substance abuser than another. Our hope is to be able to improve treatment and perhaps in the long-term even prevent this abuse," says Ditte Demontis.
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About iPSYCH

iPSYCH was founded back in 2012 when six leading researchers who all work in the field of psychiatry got together. Their mission was to find the causes of five of the most serious mental disorders; schizophrenia, bipolar disorder (previously manic depression), autism, ADHD and depression. iPSYCH's purpose was - and still is - to lay the foundations for better treatment and prevention of mental disorders by mapping the factors that play a role in these diseases.

By examining genes and risk factors in more than 80,000 Danes who both did and did not suffer from mental disorders, iPSYCH sheds light on the complex interaction between heredity factors and the environment, which for some people result in them developing a mental disorder. The project examines the disorders from various angles, ranging from genes and cells to population studies, prenatal life to adult patient and from cause to symptom.

iPSYCH is primarily funded by The Lundbeck Foundation and is a national project anchored at Aarhus University in collaboration with the University of Copenhagen, the Central Denmark Region and the Capital Region of Denmark, as well as SSI, the Danish State Serum Institute. The project's researchers collaborate with, among others: the Broad Institute, MIT/Harvard University, USA; Psychiatric Genomics Consortium, Johns Hopkins University, USA; Queensland Brain Institute, Australia; the University of California, Los Angeles, USA; deCode Genetics, Iceland; the Faroese Biobank; and 23andMe .

Today iPSYCH is one of the world's largest studies of genetic and environmental causes of mental disorders and it now comprises more than 140 researchers within psychiatry, genetics and register-based research.

Background for the results:

Type of study: iPSYCH has collected genetic information on 2,387 people diagnosed with cannabis abuse and 48,985 control subjects. Subsequently, the findings where repeated in 5,501 people who were also diagnosed with cannabis abuse and 301,041 control subjects collected by deCODE Genetics in Iceland.

Partners: deCODE Genetics from Iceland.

External funding: The study is financed by the Lundbeck Foundation and international foundations such as NIH.

The scientific article can be read in Nature Neuroscience.

Contact

Associate Professor Ditte Demontis
Aarhus University, Department of Biomedicine
Tel.: (+45) 2853 9746
Email: ditte@biomed.au.dk

Aarhus University

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