This genome-wide association study assesses analyses from 3 studies of substance use disorder genetics to identify DSM-IV criteria for cannabis dependence in a large African American and European American cohort.
This study uses data from the Avon Longitudinal Study of Parents and Children to investigate the association of genetic risk for schizophrenia with different phenotypes in a population-based birth cohort of adolescents.
This multicenter collaborative study explores whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding–related brain activity, and Alzheimer disease.
This genome-wide association analysis identifies a novel locus for neuroticism and shows polygenic association with major depressive disorder (MDD).
Liberzon et al examine the association of 3755 candidate gene SNPs with PTSD development in interaction with a history of childhood trauma. They performed a genetic association study in an Ohio National Guard longitudinal cohort, with replication in an independent Grady Trauma Project (Atlanta, Georgia) civilian cohort.
Nicodemus and colleagues assessed the association between single nucleotide polymorphisms in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and assessed whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score.
Dickinson and colleagues aimed to identify single-nucleotide polymorphisms associated with general cognitive ability in people with schizophrenia and control individuals.
Nurnberger et al identify biological pathways that contribute to risk for bipolar disorder using genes with consistent evidence for association in multiple genome-wide association studies.
Individual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive.
To investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use.
Interactions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with psychosis to examine genetic moderation of the association between Structured Interview for Schizotypy–Revised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder.
The Netherlands and Flanders, Belgium.
Eight hundred one patients with psychosis and their 740 unaffected siblings.
Significant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, case-sibling, and case-control analyses.
In the unaffected siblings, 16 SNPs in 12 genes showed significant interaction at P < .05, 3 of which survived correction for multiple testing (P < .0003), situated in AKT1 (rs2494732 and rs1130233) and LRRTM1 (rs673871). Follow-up analysis supported AKT1 rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis. In the unaffected siblings, the AKT1 × cannabis interaction explained 2.2% additional variance in schizotypy in the whole sample and 19.0% additional variance in the exposed siblings with recent cannabis use.
Genetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D2 receptor.