Most genetic risk for cannabis use disorder overlaps with genes affecting opportunity and frequency of use | Research

The takeaway

A twin study of 3,303 Australians found that cannabis use disorder is highly heritable (78%), but 83% of its genetic influences overlap with genes affecting the opportunity to use cannabis and frequency of use, with only 17% unique to the disorder itself.

Read this if you are interested in the genetics of cannabis addiction and what makes some people more vulnerable than others.

83% of genetic risk for cannabis disorder overlaps with general use genes; only 17% is disorder-specific

What the researchers found

Researchers used data from 3,303 Australian twins to decompose the genetic and environmental contributions to three stages of cannabis involvement: opportunity to use, frequency of use, and cannabis abuse/dependence.

All three stages were substantially heritable: opportunity (64%), frequency (74%), and abuse/dependence (78%). Shared environment played no significant role; the remaining variance was due to unique environmental factors.

Critically, there was extensive genetic overlap between stages. Opportunity shared 45% of its genetic influences with frequency of use. And of the genetic influences on cannabis abuse/dependence, only 17% were unique from those acting on opportunity and frequency.

This means that 83% of the genetic risk for developing a cannabis use disorder is the same genetic risk that determines whether someone has the opportunity to try cannabis and how often they use it. The disorder-specific genetics (vulnerability to lose control once using) accounts for a relatively small proportion.

Why it matters

This finding has major implications for genetic research: studies searching for genes specific to cannabis addiction will mostly find genes that affect whether someone uses cannabis at all. This means genetic studies of cannabis use disorder must carefully account for exposure to avoid misidentifying general use genes as disorder genes.

The numbers in context

Heritability: opportunity 64%, frequency 74%, abuse/dependence 78%. Shared environment ~0 for all. Opportunity shares 45% of genetic influences with frequency. Only 17% of genetic influences on abuse/dependence are unique from those acting on opportunity and frequency.

How the study worked

Trivariate Cholesky decomposition in 3,303 Australian twins measuring age of onset of cannabis use opportunity, lifetime frequency of use, and lifetime DSM-IV cannabis abuse/dependence. Estimated additive genetic (A), shared environment (C), and unique environment (E) contributions and overlap.

What this study cannot tell us

Australian twin sample may not generalize to other populations. DSM-IV criteria used (not DSM-5). Self-reported measures of opportunity, frequency, and diagnosis. Twin designs assume equal environments for identical and fraternal twins. The Cholesky decomposition assumes a specific causal ordering (opportunity -> frequency -> disorder).

How to read the evidence

Large twin study (3,303) with rigorous behavioral genetics methodology provides strong evidence on the genetic architecture of cannabis use stages.

When this study was published

Published in 2018. Genome-wide association studies have since identified specific genetic variants involved in cannabis use and use disorder.

The bigger picture

This study reframes cannabis addiction genetics. Rather than searching for genes that make someone vulnerable to addiction once they start using, most of the genetic action is in the earlier stages: who encounters cannabis, who decides to try it, and who uses it frequently. The progression from frequent use to disorder involves relatively few additional genetic factors.

Questions still open

What specific genes are in the 17% unique to cannabis use disorder? Would prevention targeting opportunity and frequency genes be more effective than targeting disorder-specific genes? Do these proportions differ across populations with different cannabis availability?

Common questions

Is cannabis addiction genetic?

Substantially. This study found 78% of the variation in cannabis abuse/dependence is attributable to genetic factors. However, most of these genes (83%) are the same ones that influence whether someone has the opportunity and inclination to use cannabis at all.

Are there specific addiction genes?

Yes, but they account for a relatively small proportion. Only 17% of the genetic influences on cannabis use disorder were unique from those affecting general cannabis use behavior. Most genetic vulnerability operates through earlier stages of use.

Read the original research

Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design.

Psychological medicine, 48(16), 2786-2793

View on PubMed ↗Publisher’s paper ↗

Citation

Hines, Lindsey A; Morley, Katherine I; Rijsdijk, Fruhling; Strang, John; Agrawal, Arpana; Nelson, Elliot C; Statham, Dixie; Martin, Nicholas G; Lynskey, Michael T. (2018). Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design.. Psychological medicine, 48(16), 2786-2793. https://doi.org/10.1017/S0033291718000478