In a recent publication in Nature Genetics, researchers conducted a comprehensive genome-wide association study (GWAS) to unravel the genetic underpinnings of cannabis use disorder. This study not only sheds light on the pathophysiology of the disorder but also underscores public health concerns associated with it.
Cannabis, a psychoactive substance historically associated with recreational use, has been linked to various health complications, including cognitive deficits, psychiatric disorders, and cancers. While some countries have embraced medicinal use and decriminalized recreational cannabis, the evolving legal landscape has led to a surge in cannabis use disorder globally.
The study employed a GWAS meta-analysis using the expansive Million Veteran Program database, encompassing genetic, health, and lifestyle data. Analysis extended across diverse ancestries, with significant findings in European, African, mixed American, and East Asian groups.
- Genomic Loci: The study identified 22 genome-wide significant loci in European ancestry, two in African, one in mixed American, and two in East Asian ancestry.
- Lead SNPs: For various ancestries, lead single nucleotide polymorphisms (SNPs) were associated with specific genes, including the cholinergic receptor nicotinic alpha 2 subunit and the semaphorin 6D-encoding gene.
- Associations: Comparative analysis highlighted substantial overlaps of cannabis use disorder with pathological and negative traits, showing stronger associations than with cannabis use traits.
- Causal Relationships: Bidirectional causal links were identified between cannabis use disorder and schizophrenia, while a unidirectional link was observed between chronic pain and cannabis use disorder. Notably, cannabis use disorder exhibited a unidirectional causal effect on lung cancer, independent of smoking initiation.
A transcriptome-wide association study revealed 36 and 15 genes associated with adult and fetal brain frontal cortex expression, respectively. DALR Anticodon Binding Domain Containing 3 (DALRD3) emerged as a common gene associated with developmental delay and early-onset epileptic encephalopathy.
The study distinguishes between cannabis use and cannabis use disorder, emphasizing the latter's stronger genetic association with psychopathology and disability. Importantly, it establishes a causal link between cannabis use disorder and an elevated risk of lung cancer, providing valuable insights into the complex interplay of genetics and health outcomes in individuals with cannabis use disorder.