Genome-wide search found no single gene strongly linked to starting cannabis use

Meta-analysis of two genome-wide association studies with over 10,000 individuals. Standard GWAS methodology was used to test associations between common genetic variants and cannabis use initiation. Gene-based testing aggregated SNP effects within genes. SNP-based heritability was estimated using genomic-relatedness-based restricted maximum likelihood (GREML).

This null result is informative. It demonstrates that cannabis initiation is not driven by any single common genetic variant of large effect. The gap between the 6% SNP-heritability and 40% twin heritability suggests that the genetics of cannabis use initiation are highly complex and distributed across many genes.

This "missing heritability" pattern is common in behavioral genetics and addiction research. It suggests that future studies will need much larger sample sizes and potentially different methodological approaches (including whole-genome sequencing to capture rare variants) to identify the specific genetic architecture of cannabis use.

Sample size, while large for its time, may have been insufficient to detect variants of very small effect. Only common genetic variants were tested. Cannabis use initiation is a complex phenotype influenced by many non-genetic factors. The study focused on initiation, not progression to regular use or dependence.