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.