S100A10 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 ( S100A10 rs72993629, p = 2.73 × 10-8 ) and a potential transpopulation signal in women ( CLTC rs12944716, p = 5.27 × 10-8 ). A resting-state fMRI follow-up analysis of S100A10 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 ( p = 7.8 × 10-3 ) and reduced power of the right pallidum in fractional ALFF analysis ( p = 4.6 × 10-3 ). The activity of these brain regions is known to be involved in sexual functions and behaviours. The S100A10 result functionally recapitulated our S100B finding observed in our previous genome-wide association study of CaD. The probability of identifying 2 S100 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 S100A10 and S100B 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.