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

Polimanti, Renato; Meda, Shashwath A.; Pearlson, Godfrey D.; Zhao, Hongyu; Sherva, Richard; Farrer, Lindsay A.; Kranzler, Henry R.

doi:10.1503/jpn.160189

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…A shared genetic liability between first use of tobacco, alcohol, and cannabis and later substance use disorder was also identified in a twin study [114]. Gene-by-environment genome-wide interaction studies have identified S100A10 and S100B as significant risk loci for cannabis use and risky sexual behavior and LHPP as a risk locus for alcohol dependence and risky sexual behavior [115,116]. The role of gender and ancestry in substance use and risky sexual behavior has also been explored, suggesting potentially different risk loci and mechanisms [115].…”

Section: Substance Use Disordermentioning

confidence: 96%

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

Musci

Augustinavicius

Volk

2019

Curr Psychiatry Rep

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Purpose of Review-We identify the recent evidence for gene-by-environment interaction studies in relation to psychiatric disorders. We focus on the key genotypic data as well as environmental exposures and how they interact to predict psychiatric disorders and psychiatric symptomatology. We direct our focus on the psychiatric outcomes that were focused on by the Psychiatric Genetics Consortium. Recent Findings-Many of the studies focus on candidate gene approaches, with most of the studies drawing upon previous literature to decide the genes of interest. Other studies used a genome-wide approach. While some studies demonstrated positive replication of previous findings, replication is still an issue within gene-by-environment interaction studies. Summary-Gene-by-environment interaction research in psychiatry globally suggests some susceptibility to environmental exposures based on genotype; however, greater clarity is needed around the idea that genetic risk may not be disorder specific.

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Section: Substance Use Disordermentioning

confidence: 96%

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

Musci

Augustinavicius

Volk

2019

Curr Psychiatry Rep

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“…Our work describes a critical role for Tmod2 in drug-induced behavioral sensitization and voluntary drug intake. Tmod2 has been weakly linked to risky drug use in humans and its gene expression and protein levels are dynamic upon drug exposure in animal models [46][47][48][49][50][51][52][53] . We provide behavioral data that Tmod2…”

Section: Discussionmentioning

confidence: 99%

“…Recent human GWAS studies have shown that Tmod2 haplotypes are associated with cognitive impairments 44,45 . In human candidate gene studies, Gelernter and colleagues showed that Tmod2 is associated with drug-dependent risk-taking behavior and proposed TMOD2-mediated remodeling of brain areas regulating sexual function and behavior 46 . In several transcriptomics and proteomics studies, Tmod2 mRNA and protein levels are differentially modulated following repeated methamphetamine [47][48][49] , alcohol 50 , cocaine 51 , or morphine 52 administration in animal models.…”

Section: Introductionmentioning

confidence: 99%

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

Mitra

Deats

Dickson

et al. 2019

Preprint

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Drugs of abuse induce neuroadaptations, including synaptic plasticity, that are critical for transition to addiction, and genes and pathways that regulate these neuroadaptations are potential therapeutic targets.Tropomodulin 2 (Tmod2) is an actin-regulating gene that plays an important role in synapse maturation and dendritic arborization and has been implicated in substance-abuse and intellectual disability in humans. Here we mine the KOMP2 data and find that Tmod2 knockout mice show emotionality phenotypes that are predictive of addiction. Detailed addiction phenotyping showed that Tmod2 deletion does not affect the acute locomotor response to cocaine administration. However, sensitized locomotor responses are highly attenuated in these knockouts, indicating a potential lack of necessary drug-induced plasticity. In addition, Tmod2 mutant animals do not self-administer cocaine indicating lack of hedonic responses to cocaine. Whole brain MR imaging shows differences in brain volume across multiple regions although transcriptomic experiments did not reveal perturbations in gene co-expression networks.Detailed electrophysiological characterization of Tmod2 KO neurons, showed increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. Cocaine-induced synaptic plasticity that is critical for sensitization is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons, providing a mechanistic explanation of the cocaine response phenotypes.Combined, these data provide compelling evidence that Tmod2 is a major regulator of plasticity in the mesolimbic system and regulates the reinforcing and addictive properties of cocaine.

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“…International Publisher addition, P11 contributes to the clinical hemorrhagic phenotypes of acute promyelocytic leukemia as a plasminogen receptor [33]. Dysregulation of P11 was also involved in cancers [34,35], fatty livers [36], cocaine reward and cannabis dependence [37,38], and Diarrhea-predominant Irritable Bowel Syndrome [39]. These studies suggested that P11 is multifunctional in regulation of development of various diseases in humans, in addition to its major roles in depression.…”

Section: Ivyspringmentioning

confidence: 99%

P11 Loss-of-Function is Associated with Decreased Cell Proliferation and Neurobehavioral Disorders in Mice

Liu¹,

Wang²,

Zheng³

et al. 2019

Int. J. Biol. Sci.

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Although depression is associated with anxiety and memory deficit in humans, the molecular mechanisms of the complication remain largely unknown. In this study, we generated P11 knockout mice using CRISPR/Cas9 technology, as well as P11 knockout MEF cell lines, and confirmed depression-like phenotype. We observed that knockout of P11 in MEFs led to a decreased cell proliferation compared with P11 +/+ MEFs. Moreover, P11 knockout resulted in a larger cell size, which resulted probably from accumulated F-actin stress fibers. The number of proliferating cells was decreased in the hippocampus of P11 KO mice. We observed anxiety-like disorder in addition to depression phenotype in the knockout mice. In addition, knockout of P11 led to memory deficit in female mice, but not in males. These data indicated that P11 is involved in regulating cell proliferation and cell size. The molecular associations of depression behavior with anxiety and memory deficit suggested a potential approach to improve therapeutic intervention through P11 in these disorders.

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

Cited by 10 publications

References 51 publications

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

P11 Loss-of-Function is Associated with Decreased Cell Proliferation and Neurobehavioral Disorders in Mice

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