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

ABSTRACT: 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.

SUBMITTER: Polimanti R

PROVIDER: S-EPMC5487272 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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<i>S100A10</i> identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours.

Polimanti Renato R Meda Shashwath A SA Pearlson Godfrey D GD Zhao Hongyu H Sherva Richard R Farrer Lindsay A LA Kranzler Henry R HR Gelernter Joel J

Journal of psychiatry & neuroscience : JPN 20170601 4

<h4>Background</h4>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).<h4>Methods</h4>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 a ...[more]

PMID: 28418321

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Project description:ImportanceCannabis dependence (CAD) is a serious problem worldwide and is of growing importance in the United States because cannabis is increasingly available legally. Although genetic factors contribute substantially to CAD risk, at present no well-established specific genetic risk factors for CAD have been elucidated.ObjectiveTo report findings for DSM-IV CAD criteria from association analyses performed in large cohorts of African American and European American participants from 3 studies of substance use disorder genetics.Design, setting, and participantsThis genome-wide association study for DSM-IV CAD criterion count was performed in 3 independent substance dependence cohorts (the Yale-Penn Study, Study of Addiction: Genetics and Environment [SAGE], and International Consortium on the Genetics of Heroin Dependence [ICGHD]). A referral sample and volunteers recruited in the community and from substance abuse treatment centers included 6000 African American and 8754 European American participants, including some from small families. Participants from the Yale-Penn Study were recruited from 2000 to 2013. Data were collected for the SAGE trial from 1990 to 2007 and for the ICGHD from 2004 to 2009. Data were analyzed from January 2, 2013, to November 9, 2015.Main outcomes and measuresCriterion count for DSM-IV CAD.ResultsAmong the 14 754 participants, 7879 were male, 6875 were female, and the mean (SD) age was 39.2 (10.2) years. Three independent regions with genome-wide significant single-nucleotide polymorphism associations were identified, considering the largest possible sample. These included rs143244591 (β = 0.54, P = 4.32 × 10-10 for the meta-analysis) in novel antisense transcript RP11-206M11.7;rs146091982 (β = 0.54, P = 1.33 × 10-9 for the meta-analysis) in the solute carrier family 35 member G1 gene (SLC35G1); and rs77378271 (β = 0.29, P = 2.13 × 10-8 for the meta-analysis) in the CUB and Sushi multiple domains 1 gene (CSMD1). Also noted was evidence of genome-level pleiotropy between CAD and major depressive disorder and for an association with single-nucleotide polymorphisms in genes associated with schizophrenia risk. Several of the genes identified have functions related to neuronal calcium homeostasis or central nervous system development.Conclusions and relevanceThese results are the first, to our knowledge, to identify specific CAD risk alleles and potential genetic factors contributing to the comorbidity of CAD with major depression and schizophrenia.

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

Publications

<i>S100A10</i> identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours.

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