A large-scale genome-wide association study meta-analysis of cannabis use disorder.

[NNadir]

The paper to which I will refer is this one: A large-scale genome-wide association study meta-analysis of cannabis use disorder, Lancet, Psychiatry, Vol 7, Is 12, P1032-1045, DECEMBER 2020

I realize that at DU, marijuana is popular with a subset of people. I am a critic of the drug, which is not to say that I support treating it as a criminal matter. I object to the claim that it is harmless, or even worse, that it's an overall positive.

Recently, citing the fact that I am greatly disturbed by my nephew's addiction to the drug - he is addicted inasmuch it is a struggle for him to stop using it - I was called out for being unscientific in employing anecdotes, in this case an anecdotal account of my nephew's problems.

Actually the scientific literature is replete with descriptions of health problems associated with marijuana abuse, which is a real thing. This should not be surprising for a psychoactive substance. This paper, which is interesting because of the exercise in gene mapping and behavioral consequences is open sourced. It is available in full text for free. It indicates that there is a genetic component for people who do get addicted, even though, there are people who can use the drug without becoming addicted. This should not be overly surprising, considering alcohol use and abuse. This does not imply treatment is impossible; only that it is often necessary.

An excerpt:

Introduction
Cannabis use is common, but most users do not progress to cannabis use disorders. About 50–70% of liability to cannabis use disorders is due to genetic factors.1 Three genome-wide association studies (GWASs) of cannabis use disorders2, 3, 4 have identified variants reaching genome-wide significance, but inadequate sample sizes (sample size from largest study to date: 51 372, with 2387 cases) and heterogeneity among samples have contributed to a paucity of replicable findings: only one locus, tagged by a cis-eQTL for CHRNA2 (encoding a nicotinic acetylcholine receptor), has been robustly identified.3

A GWAS of lifetime cannabis use (184 765 total sample size, 43 380 cases) identified eight genome-wide significant loci and 35 significant genes.5 Twin studies suggest high genetic correlations between early stages of cannabis experimentation and later cannabis use disorder.6 However, casual cannabis use is affected by a variety of socioenvironmental influences and age-period-cohort effects, whereas progression to cannabis use disorder is related to other psychopathologies. Findings have suggested partially distinct genetic causes underlying alcohol consumption and alcohol use disorder, including different genetic associations with other psychiatric disorders and traits.7, 8 Thus, in addition to examining the genomic liability for cannabis use disorder, we tested whether the genetic influences underlying cannabis use and cannabis use disorder diverge with respect to behavioural and brain measures.

Research in context

Evidence before this study

Cannabis use disorder is heritable (50–70% according to twin and family studies), yet identification of genomic variants associated with cannabis use disorder from genome-wide association studies (GWASs) remains sparse. We surveyed all peer-reviewed journal publications in English on GWASs of cannabis use disorder or cannabis dependence using Google Scholar and PubMed, published between Jan 1, 1990, and April 1, 2020. Search terms included “cannabis dependence”, “cannabis abuse”, “cannabis use disorder”, “marijuana dependence”, “marijuana abuse”, “marijuana use disorder”, and “GWAS”. The most promising finding to date is a variant that is a cis-eQTL for CHRNA2 (Demontis and colleagues), which was replicated in an independent dataset for cannabis use disorder. Independently, GWAS of cannabis use have identified multiple genetic risk loci; however, the extent to which the genetics of cannabis use correlates with liability to cannabis use disorder has not been determined. Although GWASs of cannabis use have been studied in the context of a variety of psychiatric and psychosocial correlates, it is expected that some divergent associations will be seen when looking at cannabis use disorder. Previous studies have drawn causal links between cannabis exposure and brain volume, but the relationship between genetic liability to cannabis use disorder and brain volume in individuals naive to cannabis has not yet been studied.

Added value of this study

Our study is the current largest GWAS of cannabis use disorder and the first to include a transancestral component. We found a novel risk locus on chromosome 7. The lead risk variant at this locus is an eQTL for FOXP2—a gene previously implicated in risk-taking behaviours. Contrasting cannabis use and cannabis use disorder, we found that increased liability for cannabis use disorder is genetically correlated with low educational attainment, early age at first birth, and high body-mass index, traits that show opposite directions of association with lifetime cannabis ever-use. We also found that genetic liability for cannabis use disorder is associated with increased risk of mental health problems, infectious diseases, and respiratory illnesses in a large independent sample. Finally, we found a significant association between increased polygenic liability for cannabis use disorder and low white matter volume in cannabis-naive children, suggesting a potential role of cannabis-related genetic predisposition in early brain development...

And so on. It is as difficult sometimes at DU to criticize marijuana use, just as it is difficult and controversial to criticize so called "renewable energy."

Nonetheless, my liberalism is not connected with lockstep fondness for certain activities or practices, but is rather connected to my values for a sustainable world, with a healthy and well informed populace, living in an environment of opportunity and tolerance, free of the weight of bigotry, brutality and injustice.

I am not by any means a genetic reductionist, genetic reductionism often translating into racism; I believe we drive our genes rather than having our genes drive us; but I do believe that we should be aware of predispositions our genes enhance that we must learn to manage. (I do hope my nephew will overcome his addiction; I know it is possible.)

The article is open for anyone to read; the author list is rather long.

If someone would like to object to it; and I'm sure people will be so inclined if experience at DU teaches me anything, fire away.

It is what it is.

Have a nice day tomorrow.