A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men

Abstract

Background Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. Methods We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male–male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. Results A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18–20% of the variance in liability, were non-specific. Conclusions In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA.

The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study.

“…Patterns of cannabis use such as lifetime cannabis use (never/ever used) and Cannabis Use Disorder (CUD) are influenced by genetic factors 9,10 . Twin heritability reaches 45% for lifetime cannabis use and 51% to 70% for CUD 11,12 . Genome wide Association Studies (GWAS) have also shown a significant genetic correlation between lifetime cannabis use and CUD on the one hand, and schizophrenia on the other 13 .…”

Genome-wide association study implicatesCHRNA2in cannabis use disorder

“…Cannabis use is increasing in the population [4][5][6] and among users around 9% become dependent 7 . The genetic risk component is high with heritability estimates of 51 8 -70% 9 . Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31x10 -12 ) that replicates in an independent population (P replication =3.27x10 -3 , P metaanalysis =9.09x10 -12 ) based on genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls.…”

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls

“…Previous studies in non-psychotic populations (Kendler & Prescott, 1998;Kendler et al 2000Kendler et al , 2015 highlight that a combination of genetic and environmental factors influence cannabis use. Patients with psychosis are more likely to use cannabis than the general population (D 'Souza, 2007) but psychosis-prone individuals are not more likely to use cannabis (Henquet et al 2005).…”