A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans
Zhongshan Cheng, Chureerat Phokaew, Yi-Ling Chou, Dongbing Lai, Jacquelyn L. Meyers, Arpana Agrawal, Lindsay A. Farrer, Henry R. Kranzler, Joel Gelernter
Translational Psychiatry November 18, 2019 DOI: 10.1038/s41398-019-0639-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Genome-wide association study with meta-analysis Peer reviewed |
|---|---|
| Sample size | 4,291 |
| Population | Long-term cannabis users (used cannabis ≥1 year and ≥100 times) of European American and African American ancestry |
| Topics | Cannabis |
| Keywords | Genome-wide association study Meta-analysis Single-nucleotide polymorphism Population Locus genetics Genotype |
| Citations | 4 |
| Key findings | A genome-wide significant association between cannabis-induced hallucinations and the CHRM3 locus was found in European Americans, with the risk allele linked to lower CHRM3 expression in the thalamus. |
Abstract
Abstract Cannabis, the most widely used illicit drug, can induce hallucinations. Our understanding of the biology of cannabis-induced hallucinations (Ca-HL) is limited. We used the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) to identify cannabis-induced hallucinations (Ca-HL) among long-term cannabis users (used cannabis ≥1 year and ≥100 times). A genome-wide association study (GWAS) was conducted by analyzing European Americans (EAs) and African Americans (AAs) in Yale-Penn 1 and 2 cohorts individually, then meta-analyzing the two cohorts within population. In the meta-analysis of Yale-Penn EAs ( n = 1917), one genome-wide significant (GWS) signal emerged at the CHRM3 locus, represented by rs115455482 ( P = 1.66 × 10 −10 ), rs74722579 ( P = 2.81 × 10 −9 ), and rs1938228 ( P = 1.57 × 10 −8 ); signals were GWS in Yale-Penn 1 EAs ( n = 1092) and nominally significant in Yale-Penn 2 EAs ( n = 825). Two SNPs, rs115455482 and rs74722579, were available from the Collaborative Study on the Genetics of Alcoholism data (COGA; 3630 long-term cannabis users). The signals did not replicate, but when meta-analyzing Yale-Penn and COGA EAs, the two SNPs’ association signals were increased (meta- P -values 1.32 × 10 −10 and 2.60 × 10 −9 , respectively; n = 4291). There were no significant findings in AAs, but in the AA meta-analysis ( n = 3624), nominal significance was seen for rs74722579. The rs115455482*T risk allele was associated with lower CHRM3 expression in the thalamus. CHRM3 was co-expressed with three psychosis risk genes ( GABAG2 , CHRNA4 , and HRH3 ) in the thalamus and other human brain tissues and mouse GABAergic neurons. This work provides strong evidence for the association of CHRM3 with Ca-HL and provides insight into the potential involvement of thalamus for this trait.
Comparable studies
Other systematic reviews and meta-analyses on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of cannabis use on outcomes of psychotic disorders: systematic review People with psychotic disorders, as examined in 13 longitudinal studies | 2008 | Systematic review | |
| The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample Patients with established schizophrenia (meta-analysis: 572) and patients with... | 2010 | Meta-analysis and cross-sectional observational study | n = 700 |
| Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review | 2020 | Systematic review | |
| Neuroimaging in cannabis use: a systematic review of the literature Cannabis users and controls in neuroimaging studies | 2009 | Systematic review | |
| Human Laboratory Studies on Cannabinoids and Psychosis. Healthy human subjects and individuals with schizophrenia | 2016 | Systematic review |