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Genetics and Genomics of Addiction
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Genetics and Genomics of Addiction

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 25226

Special Issue Editor

Dr. Jason Bubier

E-Mail Website
Guest Editor
Center for Addiction Biology, The Jackson Laboratory, 600 Main St, Bar Harbor, ME 04609, USA
Interests: genetics; addiction; behavior; microbiome; integrative functional genomics

Special Issue Information

Dear Colleagues,

With the opioid epidemic occurring during the global COVID-19 pandemic, substance use disorder (SUD) has been on the rise. Thankfully addiction can be treated and managed, but we have a limited armamentarium. Our current research on the genetic susceptibility to addiction contributes to our understanding of the mechanisms that underlie SUD. These mechanisms lie at the heart of the development of novel pharmacotherapies to facilitate the treatment of SUD.

The aim of this Special Issue is to bring together researchers of substance use disorder across various drugs of abuse and experimental systems to describe the current status of addiction genetics. Psychiatric disorders are known to be complex traits due to their polygenic nature. Substance use disorder is unique in that the progression to disease requires an exposure to an environmental factor, a drug. Sequenced genomes, new animal model resources, and GWAS of large sample sizes have made vast inroads into our understanding of the genetics that underlie addiction. Future mechanistic studies will be driven by integrating big data produced across animal models and human studies to identify their consilient features. This issue will cover topics related to genes, genetics and genomics of addiction, including but not limited to: human genetics, systems genetics, gene expression, -omics, bioinformatics, cross-species analysis, animal models, genetic mapping, candidate gene studies, GxE. We welcome researchers from across the world to contribute their high-quality manuscripts covering all the aspects related to the genetics of addiction. In this Special Issue, both original articles and reviews are welcome.

Dr. Jason Bubier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Addiction
  • Drug abuse
  • Human genetics
  • Systems genetics
  • Gene expression
  • Bioinformatics
  • Cross-species analysis
  • Animal models
  • Genomics
  • Genetic mapping

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Published Papers (7 papers)

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Editorial

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2 pages, 160 KiB  
Editorial
Genetics and Genomics of Addiction
by Jason A. Bubier
Genes 2023, 14(9), 1760; https://doi.org/10.3390/genes14091760 - 4 Sep 2023
Viewed by 1570
Abstract
Substance use disorders (SUD), like many neuropsychiatric conditions, are a heterogeneous group of disorders with similar symptomatology but often different pathoetiology [...] Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)

Research

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17 pages, 5301 KiB  
Article
The Impact of Sex, Circadian Disruption, and the ClockΔ19/Δ19 Genotype on Alcohol Drinking in Mice
by Abanoub Aziz Rizk, Bryan W. Jenkins, Yasmine Al-Sabagh, Shahnaza Hamidullah, Cristine J. Reitz, Mina Rasouli, Tami A. Martino and Jibran Y. Khokhar
Genes 2022, 13(4), 701; https://doi.org/10.3390/genes13040701 - 15 Apr 2022
Cited by 7 | Viewed by 3215
Abstract
Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in [...] Read more.
Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., ClockΔ19/Δ19 mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male ClockΔ19/Δ19 mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, ClockΔ19/Δ19 mice displayed increased alcohol consumption and preference. Sex differences were not apparent in ClockΔ19/Δ19 mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the Clock gene greatly increases alcohol consumption and abolishes sex differences present in WT animals. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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17 pages, 2241 KiB  
Article
New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork
by Alisha Chunduri, Pamela M. Watson and David G. Ashbrook
Genes 2022, 13(4), 614; https://doi.org/10.3390/genes13040614 - 29 Mar 2022
Cited by 2 | Viewed by 3344
Abstract
Gene-by-environment interactions are important for all facets of biology, especially behaviour. Families of isogenic strains of mice, such as the BXD strains, are excellently placed to study these interactions, as the same genome can be tested in multiple environments. BXD strains are recombinant [...] Read more.
Gene-by-environment interactions are important for all facets of biology, especially behaviour. Families of isogenic strains of mice, such as the BXD strains, are excellently placed to study these interactions, as the same genome can be tested in multiple environments. BXD strains are recombinant inbred mouse strains derived from crossing two inbred strains—C57BL/6J and DBA/2J mice. Many reproducible genometypes can be leveraged, and old data can be reanalysed with new tools to produce novel insights. We obtained drug and behavioural phenotypes from Philip et al. Genes, Brain and Behaviour 2010, and reanalysed their data with new genotypes from sequencing, as well as new models (Genome-wide Efficient Mixed Model Association (GEMMA) and R/qtl2). We discovered QTLs on chromosomes 3, 5, 9, 11, and 14, not found in the original study. We reduced the candidate genes based on their ability to alter gene expression or protein function. Candidate genes included Slitrk6 and Cdk14. Slitrk6, in a Chromosome14 QTL for locomotion, was found to be part of a co-expression network involved in voluntary movement and associated with neuropsychiatric phenotypes. Cdk14, one of only three genes in a Chromosome5 QTL, is associated with handling induced convulsions after ethanol treatment, that is regulated by the anticonvulsant drug valproic acid. By using families of isogenic strains, we can reanalyse data to discover novel candidate genes involved in response to drugs of abuse. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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16 pages, 1850 KiB  
Article
Gnas Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats
by Peng Liu, Jialong Liang, Fengze Jiang, Wanshi Cai, Fang Shen, Jing Liang, Jianjun Zhang, Zhongsheng Sun and Nan Sui
Genes 2022, 13(3), 553; https://doi.org/10.3390/genes13030553 - 21 Mar 2022
Cited by 6 | Viewed by 2844
Abstract
Impairing reconsolidation may disrupt drug memories to prevent relapse, meanwhile long-term transcription regulations in the brain regions contribute to the occurrence of emotional memories. The basolateral amygdala (BLA) is involved in the drug-cue association, while the nucleus accumbens (NAc) responds to the drug [...] Read more.
Impairing reconsolidation may disrupt drug memories to prevent relapse, meanwhile long-term transcription regulations in the brain regions contribute to the occurrence of emotional memories. The basolateral amygdala (BLA) is involved in the drug-cue association, while the nucleus accumbens (NAc) responds to the drug reward. Here, we assessed whether DNA methyltransferases (Dnmts) in these two brain regions function identically in the reconsolidation of morphine reward memory. We show that Dnmts inhibition in the BLA but not in the NAc after memory retrieval impaired reconsolidation of a morphine reward memory. Moreover, the mRNA levels of Dnmt3a and Dnmt3b, rather than Dnmt1, in the BLA were continuously upregulated after retrieval. We further identified the differentially methylated regions (DMRs) in genes in the BLA after retrieval, and focused on the DMRs located in gene promoter regions. Among them were three genes (Gnas, Sox10, and Pik3r1) involved in memory modulation. Furthermore, Gnas promoter hypermethylation was confirmed to be inversely correlated with the downregulation of Gnas mRNA levels. The findings indicate that the specific transcription regulation mechanism in the BLA and NAc on reconsolidation of opiate-associated memories can be dissociable, and DNA hypermethylation of Gnas in the BLA is necessary for the reconsolidation of morphine reward memories. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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12 pages, 603 KiB  
Article
Analysis of Relationships between DAT1 Polymorphism Variants, Personality Dimensions, and Anxiety in New Psychoactive Substance (Designer Drug) (NPS) Users
by Jolanta Chmielowiec, Krzysztof Chmielowiec, Jolanta Masiak, Tomasz Pawłowski, Dariusz Larysz and Anna Grzywacz
Genes 2021, 12(12), 1977; https://doi.org/10.3390/genes12121977 - 10 Dec 2021
Cited by 4 | Viewed by 2609
Abstract
The use of ‘new psychoactive substances’ appears to be increasingly common. The aim of this study was to examine biological and personality determinants in individuals who choose to use these substances, which may help in the prevention and treatment of psychoactive substance use [...] Read more.
The use of ‘new psychoactive substances’ appears to be increasingly common. The aim of this study was to examine biological and personality determinants in individuals who choose to use these substances, which may help in the prevention and treatment of psychoactive substance use disorders. The study group consisted of 374 male volunteers; all were users of ‘new psychoactive substances’ (NPS). The NPS users were recruited after they had abstained—for at least 3 months—from any substance of abuse in addiction treatment facilities. The NPS patients and the control subjects were examined by a psychiatrist using the Mini-International Neuropsychiatric Interview (M.I.N.I.), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) scales. The real-time PCR method was used for genotyping. When we compared the controls with the study group, statistically significant interactions were found between DAT1 polymorphism, neuroticism, and NPS use. NPS use and DAT1 polymorphism were associated with a higher level of neuroticism on the NEO-FFI scale. The study group of NPS users showed a higher severity of anxiety symptoms, both in terms of trait and state, compared to the control group. The results may support the idea that neuroticism and anxiety correlate strongly with coping motives for using NPS. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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7 pages, 443 KiB  
Article
Association of PIP4K2A Polymorphisms with Alcohol Use Disorder
by Olga Yu. Fedorenko, Ekaterina V. Mikhalitskaya, Valentina A. Toshchakova, Anton J. M. Loonen, Nikolay A. Bokhan and Svetlana A. Ivanova
Genes 2021, 12(10), 1642; https://doi.org/10.3390/genes12101642 - 19 Oct 2021
Cited by 4 | Viewed by 2099
Abstract
Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the [...] Read more.
Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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Review

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13 pages, 250 KiB  
Review
Genetic Influences on Fetal Alcohol Spectrum Disorder
by Danielle Sambo and David Goldman
Genes 2023, 14(1), 195; https://doi.org/10.3390/genes14010195 - 12 Jan 2023
Cited by 18 | Viewed by 8192
Abstract
Fetal alcohol spectrum disorder (FASD) encompasses the range of deleterious outcomes of prenatal alcohol exposure (PAE) in the affected offspring, including developmental delay, intellectual disability, attention deficits, and conduct disorders. Several factors contribute to the risk for and severity of FASD, including the [...] Read more.
Fetal alcohol spectrum disorder (FASD) encompasses the range of deleterious outcomes of prenatal alcohol exposure (PAE) in the affected offspring, including developmental delay, intellectual disability, attention deficits, and conduct disorders. Several factors contribute to the risk for and severity of FASD, including the timing, dose, and duration of PAE and maternal factors such as age and nutrition. Although poorly understood, genetic factors also contribute to the expression of FASD, with studies in both humans and animal models revealing genetic influences on susceptibility. In this article, we review the literature related to the genetics of FASD in humans, including twin studies, candidate gene studies in different populations, and genetic testing identifying copy number variants. Overall, these studies suggest different genetic factors, both in the mother and in the offspring, influence the phenotypic outcomes of PAE. While further work is needed, understanding how genetic factors influence FASD will provide insight into the mechanisms contributing to alcohol teratogenicity and FASD risk and ultimately may lead to means for early detection and intervention. Full article
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
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