Exploring Phenotypic and Genetic Overlap Between Cannabis Use and Schizotypy

Abstract

There is a well-established relationship between cannabis use and psychosis, although the exact nature of this relationship is not fully understood. Recent studies have observed significant genetic overlap between a diagnosis of schizophrenia and lifetime cannabis use. Expanding on this work, the current study aimed to examine whether genetic overlap also occurs for subclinical psychosis (schizotypy) and cannabis use, as well as examining the phenotypic association between the traits. Phenotypic correlations were calculated for a variety of schizotypy and cannabis phenotypes in the UK Biobank (UKB), and single nucleotide polymorphism (SNP)-based heritability estimates and genetic correlations were calculated for these UKB phenotypes as well as for several other variables taken from recent genomewide association studies. Positive phenotypic correlations were observed between 11 out of 12 pairs of the cannabis use and schizotypy phenotypes (correlation range .05–.18), indicating a robust association between increased symptoms of schizotypy and cannabis use. SNP-based heritability estimates for two schizotypy phenotypes remained significant after multiple testing correction: social anhedonia (h2SNP = .08, SE = .02, N = 4025) and ever seen an unreal vision (h2SNP = .35, SE = .10, N = 150,717). Finally, one significant genetic correlation was observed between schizotypy and cannabis use, a negative correlation between social anhedonia and number of times used cannabis (rg = −.30, p = .012). The current study suggests the relationship between cannabis use and psychosis is also seen in subclinical symptoms of psychosis, but further research with larger samples is needed to determine the biological mechanisms underlying this association.

Nongenetic Factors Associated With Psychotic Experiences Among UK Biobank Participants

“…In accordance with a previous UKB finding that showed positive genetic correlations between psychotic experiences and mental disorders, our findings suggest a shared genetic etiology between psychotic experiences and behavioral phenotypes (eg, ever contemplated self-harm; ever had prolonged feelings of sadness or depression; and ever saw a psychiatrist for nerves, anxiety, tension, or depression). Furthermore, we replicated recent UKB findings showing no statistically significant genetic correlation between cannabis use and individual psychotic experience items . This is in contrast to several studies suggesting genetic correlation between substance use (eg, smoking, drinking, and cannabis use) and psychiatric disorders, including schizophrenia.…”

“…Furthermore, we replicated recent UKB findings showing no statistically significant genetic correlation between cannabis use and individual psychotic experience items. 63 This is in contrast to several studies suggesting genetic correlation between substance use (eg, smoking, drinking, and cannabis use 52,54,61,[64][65][66] ) and psychiatric disorders, including schizophrenia. Other exposures that were previously found to be genetically correlated with schizophrenia in the UKB, such as population density 67,68 and dietary intake, 69 either failed the quality-control steps or did not reach significance in the XWAS.…”

Regional Genetic Architecture of the Corpus Callosum and its Overlap with Psychiatric and Substance Use Phenotypes

“…Cannabis use and SCZ exhibited the similar patterns of overlap with the CC, emphasizing the complex interplay between these phenotypes. The observed genetic overlap here suggests shared risk variants, potentially influencing how individuals may be predisposed to both conditions (Vaissiere et al, 2020). Cannabis use has also been associated with changes in the CC microstructural organization, particularly in patients with first episode psychosis (Rigucci et al, 2016).…”

Cannabis’s Link to Schizotypy: Phenomenon, Measurement Bias, or Delusion?

“…Psychotic illnesses covary with cannabis use in a dosedependent fashion and those afflicted tend to fare poorly if they use cannabis (Hasan et al, 2020). Recent heritability research reveals that lifetime cannabis use and SPD share considerable genetic overlap (Vaissiere et al, 2020), mirroring comparable findings with schizophrenia (Verweij et al, 2017). Nevertheless, despite identification of recent longitudinal links between cannabis use early in life and subsequent development of schizophrenia (Di Forti et al, 2019), links between SPD and schizophrenia are not clear.…”