S100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours

Renato Polimanti, Shashwath A. Meda, Godfrey D. Pearlson, Hongyu Zhao, Richard Sherva, Lindsay A. Farrer, Henry R. Kranzler, Joel Gelernter
2017 Journal of Psychiatry & Neuroscience  
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
more » ... rotected 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. S100A10 identified in a genome-wide gene × CaD interaction analysis of RSB J Psychiatry Neurosci 2017;42(4)
doi:10.1503/jpn.160189 fatcat:nupsyc5g7jcm7b5xi4uquyzvfe