identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours.

Background: We conducted a genome-wide gene × environment interaction analysis to identify genetic variants that interact with cannabis dependence (CaD) in influencing risky sexual behaviours (RSB).

Methods: Our sample included cannabis-exposed and sexually experienced African-American and European-American participants. A DSM-IV CaD diagnosis and RSB were evaluated using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We analyzed RSBs as a score that takes into account experiences of unprotected sex and multiple sexual partners.

Results: A total of 3350 people participated in our study; 43% had a CaD diagnosis, 56% were African-American and 33% were women. We identified a genome-wide significant locus in African-American participants ( rs72993629, = 2.73 × 10) and a potential transpopulation signal in women ( rs12944716, = 5.27 × 10). A resting-state fMRI follow-up analysis of rs72993629 conducted in an independent cohort showed 2 significant associations: reduced power of the left paracentral lobule in amplitude of low frequency fluctuations (ALFF) analysis ( = 7.8 × 10) and reduced power of the right pallidum in fractional ALFF analysis ( = 4.6 × 10). The activity of these brain regions is known to be involved in sexual functions and behaviours. The result functionally recapitulated our finding observed in our previous genome-wide association study of CaD. The probability of identifying 2 genes in 2 independent genome-wide investigations by chance is approximately 1 in 1.1 million.

Limitations: We were not able to identify any African-American cohort with appropriate sample size, and phenotypic assessment is available to replicate our findings.

Conclusion: The and genes, which are located on different chromosomes, encode specialized calcium-binding proteins. These data support a role for calcium homeostasis in individuals with CaD and its induced behaviours.