June 30, 2014. Genetic variants that increase risk for schizophrenia also increase the chance that a person will use cannabis, according to a study published online June 23 in Molecular Psychiatry. The study, led by Robert Power of the Institute of Psychiatry at Kingís College London, UK, examines the well-established association between schizophrenia and cannabis in 2,082 healthy people. The researchers found that those with a greater burden of schizophrenia risk variants were more likely to use cannabis, and more frequently, than those with a lesser burden.
The findings point to difficulties in teasing apart genetic from environmental influences on risk for a complex disorder. What may seem like a straightforward environmental factor may well have a genetic component, which could drive a person toward certain environments or exposures in the first place.
People with schizophrenia use cannabis more than the general population, and prospective studies find that cannabis use increases risk for psychosis (see SRF related news report). This suggests that cannabis use is one of several causal factors leading to the disorder. But others have proposed that the association between schizophrenia and cannabis stems from self-medication, or from the fact that people who are psychotic are just more inclined to partake in an illicit drug.
The new study provides yet another perspective by finding that genetic predisposition for schizophrenia can also account for some amount of cannabis use. Though the study does not rule out a role for cannabis in directly increasing risk for psychosis, it provides another example of how different outcomes (schizophrenia, cannabis use) can share some of the same genetic roots.
Of burdens and buds
First author Power and colleagues began by tallying, for each person, the burden of common risk variants for schizophrenia based on the single nucleotide polymorphisms (SNPs) identified by the Psychiatric Genomics Consortiumís latest genomewide association study (see SRF related news report). This resulted in a polygene score for each person, which reflects the combined effects of many genes toward risk for schizophrenia.
Those with the highest polygene scores were more likely to have used cannabis, whereas those with the lowest scores were not more likely to have done so. This association was strongest for polygene scores based on SNPs that had attained p values of 0.01 or lower in the previous GWAS. At this level, however, the polygene score explained a fraction (0.47 percent) of the variance in cannabis use. A significant positive correlation also emerged for the amount of cannabis use, but again accounting for a small portion of variance (0.85 percent).
The relationship between genetic risk for schizophrenia and cannabis use also held true in a separate group of 990 twin pairs. Pairs in which both twins reported using cannabis had the highest polygene scores; those in which only one twin used cannabis had middling scores; and those in which neither twin reported cannabis use had the lowest scores.
The authors note that the SNPs used to calculate the polygenic scores may not purely reflect schizophrenia risk, since it is possible that, in the GWAS samples, more cases than controls used cannabis. This means that some of the schizophrenia risk alleles identified to date may actually tag a personís predilection for cannabis. Still, the findings suggest that the association between cannabis use and schizophrenia is a two-way street, and that both directions may be at work in schizophrenia.óMichele Solis.
Power RA, Verweij KJ, Zuhair M, Montgomery GW, Henders AK, Heath AC, Madden PA, Medland SE, Wray NR, Martin NG. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry . 2014 Jun 24. Abstract