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Article ; Online: Collaborative study on the genetics of alcoholism: The strength of collaboration, team science, and longitudinal data.

Ehringer, Marissa A

2023 Volume 22, Issue 5, Page(s) e12866

Abstract: This issue contains a series of articles describing the various resources, studies, results, and future directions for the collaborative study on the genetics of alcoholism (COGA). The collaborative and integrative approach initiated by this group ~30 ... ...

Abstract	This issue contains a series of articles describing the various resources, studies, results, and future directions for the collaborative study on the genetics of alcoholism (COGA). The collaborative and integrative approach initiated by this group ~30 years ago serves as an excellent example of the strength of team science. Individually, various aspects of COGA would be limited in their impact toward improved understanding of alcohol use disorder. Collectively, their wholistic approach which spans deep longitudinal phenotypic assessments in families to include the application of large-scale omics technologies and cell-culture based molecular studies has demonstrated the power of working together.
MeSH term(s)	Humans ; Alcoholism/genetics ; Interdisciplinary Research ; Alcohol Drinking ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2023-09-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12866
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Article ; Online: Identifying epigenetic targets underlying the effects of prenatal exposure to opioids.

Ehringer, Marissa A

Genes, brain, and behavior

2019 Volume 18, Issue 6, Page(s) e12503

MeSH term(s)	Analgesics, Opioid ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Infant ; Mothers ; Pregnancy ; Prenatal Exposure Delayed Effects ; Receptors, Opioid, mu
Chemical Substances	Analgesics, Opioid ; OPRM1 protein, human ; Receptors, Opioid, mu
Language	English
Publishing date	2019-07-04
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12503
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Article ; Online: Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.

Duffy, Eamonn P / Bachtell, Ryan K / Ehringer, Marissa A

Neuroscience and biobehavioral reviews

2023 Volume 156, Page(s) 105487

Abstract: Opioid use disorder (OUD) is a worldwide public health crisis with few effective treatment options. Traditional genetics and neuroscience approaches have provided knowledge about biological mechanisms that contribute to OUD-related phenotypes, but the ... ...

Abstract	Opioid use disorder (OUD) is a worldwide public health crisis with few effective treatment options. Traditional genetics and neuroscience approaches have provided knowledge about biological mechanisms that contribute to OUD-related phenotypes, but the complexity and magnitude of effects in the brain and body remain poorly understood. The gut-brain axis has emerged as a promising target for future therapeutics for several psychiatric conditions, so characterizing the relationship between host genetics and the gut microbiome in the context of OUD will be essential for development of novel treatments. In this review, we describe evidence that interactions between host genetics, the gut microbiome, and immune signaling likely play a key role in mediating opioid-related phenotypes. Studies in humans and model organisms consistently demonstrated that genetic background is a major determinant of gut microbiome composition. Furthermore, the gut microbiome is susceptible to environmental influences such as opioid exposure. Additional work focused on gene by microbiome interactions will be necessary to gain improved understanding of their effects on OUD-related behaviors.
MeSH term(s)	Humans ; Gastrointestinal Microbiome/genetics ; Analgesics, Opioid ; Opioid-Related Disorders/genetics ; Microbiota ; Brain
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2023.105487
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Article ; Online: Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.

Romero Villela, Pamela N / Evans, Luke M / Palviainen, Teemu / Border, Richard / Kaprio, Jaakko / Palmer, Rohan H C / Keller, Matthew C / Ehringer, Marissa A

Drug and alcohol dependence

2024 Volume 257, Page(s) 111126

Abstract: Background: The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, ... ...

Abstract	Background: The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, epistatic, and gene-environment interactions. Methods: To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome. Results: Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230, that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000-2011. Conclusions: To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes.
MeSH term(s)	Humans ; Chromosomes, Human, Pair 20 ; Membrane Proteins/genetics ; Parkinson Disease ; Smoking/genetics ; Tobacco Products ; Polymorphism, Single Nucleotide/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease
Chemical Substances	Membrane Proteins
Language	English
Publishing date	2024-02-15
Publishing country	Ireland
Document type	Meta-Analysis ; Journal Article
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2024.111126
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Article ; Online: Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Duffy, Eamonn P / Ward, J O / Hale, L H / Brown, K T / Kwilasz, Andrew J / Saba, Laura M / Ehringer, Marissa A / Bachtell, Ryan K

Genes, brain, and behavior

2024 Volume 23, Issue 2, Page(s) e12894

Abstract: Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide ... ...

Abstract	Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h
MeSH term(s)	Rats ; Animals ; Oxycodone/pharmacology ; Analgesics, Opioid/pharmacology ; Analgesia ; Opioid-Related Disorders
Chemical Substances	Oxycodone (CD35PMG570) ; Analgesics, Opioid
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12894
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Article ; Online: South Asia: The Missing Diverse in Diversity.

Dokuru, Deepika R / Horwitz, Tanya B / Freis, Samantha M / Stallings, Michael C / Ehringer, Marissa A

Behavior genetics

2023 Volume 54, Issue 1, Page(s) 51–62

Abstract: South Asia, making up around 25% of the world's population, encompasses a wide range of individuals with tremendous genetic and environmental diversity. This region, which spans eight countries, is home to over 4500 anthropologically defined groups that ... ...

Abstract	South Asia, making up around 25% of the world's population, encompasses a wide range of individuals with tremendous genetic and environmental diversity. This region, which spans eight countries, is home to over 4500 anthropologically defined groups that speak numerous languages and have an array of religious beliefs and cultures, making it one of the most diverse places in the world. Much of the region's rich genetic diversity and structure is the result of a complex combination of population history, migration patterns, and endogamous practices. Despite the overwhelming size and diversity, South Asians have often been underrepresented in genetic research, making up less than 2% of the participants in genetic studies. This has led to a lack of population specific understanding of genetic disease risks. We aim to raise awareness about underlying genetic diversity in this ancestry group, call attention to the lack of representation of the group, and to highlight strategies for future studies in South Asians.
MeSH term(s)	Humans ; Asia, Southern ; Asian People/genetics ; Biomedical Research ; Cultural Diversity
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	280238-7
ISSN	1573-3297 ; 0005-7851 ; 0001-8244
ISSN (online)	1573-3297
ISSN	0005-7851 ; 0001-8244
DOI	10.1007/s10519-023-10161-y
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Article ; Online: Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.

Evans, Luke M / Arehart, Christopher H / Grotzinger, Andrew D / Mize, Travis J / Brasher, Maizy S / Stitzel, Jerry A / Ehringer, Marissa A / Hoeffer, Charles A

PLoS genetics

2023 Volume 19, Issue 5, Page(s) e1010693

Abstract: It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all ... ...

Abstract	It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and replicate (in independent cohorts) several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene set enrichment of TWIS associations (E-TWIS), finding numerous pathways and networks enriched in interaction associations. Epistasis is may be widespread, and our procedure represents a tractable framework for beginning to explore gene interactions and identify novel genomic targets.
MeSH term(s)	Transcriptome/genetics ; Epistasis, Genetic ; Multifactorial Inheritance/genetics ; Gene Regulatory Networks/genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study/methods
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010693
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Article ; Online: Testing associations between human anxiety and genes previously implicated by mouse anxiety models.

Brasher, Maizy S / Mize, Travis J / Thomas, Aimee L / Hoeffer, Charles A / Ehringer, Marissa A / Evans, Luke M

Genes, brain, and behavior

2023 Volume 22, Issue 6, Page(s) e12851

Abstract: Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral ... ...

Abstract	Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral models of anxiety, yet it is unclear the extent to which genes identified in these experimental systems contribute to genetic variation in human anxiety phenotypes. Leveraging new and existing large-scale human genome-wide association studies, we tested whether sets of genes previously identified in mouse anxiety-like behavior studies contribute to a range of human anxiety disorders. When tested as individual genes, 13 mouse-identified genes were associated with human anxiety phenotypes, suggesting an overlap of individual genes contributing to both mouse models of anxiety-like behaviors and human anxiety traits. When genes were tested as sets, we did identify 14 significant associations between mouse gene sets and human anxiety, but the majority of gene sets showed no significant association with human anxiety phenotypes. These few significant associations indicate a need to identify and develop more translatable mouse models by identifying sets of genes that "match" between model systems and specific human phenotypes of interest. We suggest that continuing to develop improved behavioral paradigms and finer-scale experimental data, for instance from individual neuronal subtypes or cell-type-specific expression data, is likely to improve our understanding of the genetic etiology and underlying functional changes in anxiety disorders.
MeSH term(s)	Humans ; Mice ; Animals ; Genome-Wide Association Study ; Anxiety Disorders/genetics ; Anxiety/genetics ; Phenotype
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12851
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Article ; Online: Reinvigoration of a Diversity, Equity, and Inclusion Committee at the Institute for Behavioral Genetics: Student-driven Progress.

Paulich, Katie N / Horwitz, Tanya B / Freis, Samantha M / Romero Villela, Pamela N / Aki, Sidney / Stallings, Michael C / Ehringer, Marissa A

Behavior genetics

2023 Volume 54, Issue 1, Page(s) 24–33

Abstract: Extremist far-right ideologies, including scientifically inaccurate beliefs about race, are on the rise (Mieriņa and Koroļeva 2015; Youngblood 2020); individuals perpetuating such ideologies occasionally cite genetics research, including behavioral ... ...

Abstract	Extremist far-right ideologies, including scientifically inaccurate beliefs about race, are on the rise (Mieriņa and Koroļeva 2015; Youngblood 2020); individuals perpetuating such ideologies occasionally cite genetics research, including behavioral genetics research. This highlights the need for behavioral geneticists to actively confront extremist ideology and promote anti-racism. We emphasize the need for Diversity, Equity and Inclusion (DEI) committees within behavioral genetics institutions. DEI committees can lead to: greater awareness of ways in which behavioral genetics has been misused (historically and currently) to harm minoritized communities, increased discussions on conducting ethical behavioral genetics research, and increased collaboration for conducting more diverse behavioral genetics research. We discuss the activities and goals of the student-driven DEI committee at the Institute for Behavior Genetics (IBG). At the same time, we acknowledge we have a long way to go, both as a committee and as a field. Our committee is still in its early stages; we discuss challenges to increasing DEI in the field and present future goals for both IBG and the behavioral genetics community as we explore the process of implementing DEI work.
MeSH term(s)	Humans ; Diversity, Equity, Inclusion ; Students
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	280238-7
ISSN	1573-3297 ; 0005-7851 ; 0001-8244
ISSN (online)	1573-3297
ISSN	0005-7851 ; 0001-8244
DOI	10.1007/s10519-023-10149-8
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Article ; Online: Diazepam effects on anxiety-related defensive behavior of male and female high and low open-field activity inbred mouse strains.

Mehrhoff, Erika A / Booher, Winona C / Hutchinson, Julianna / Schumacher, Grace / Borski, Curtis / Lowry, Christopher A / Hoeffer, Charles A / Ehringer, Marissa A

Physiology & behavior

2023 Volume 271, Page(s) 114343

Abstract: Open-field activity is a commonly used measure of anxiety-related behavior in rodents. The inbred High and Low Activity strains of mice, selected for extreme differences in open-field activity, have been used as a genetic model of anxiety-related ... ...

Abstract	Open-field activity is a commonly used measure of anxiety-related behavior in rodents. The inbred High and Low Activity strains of mice, selected for extreme differences in open-field activity, have been used as a genetic model of anxiety-related behaviors. These selected strains have been thoroughly studied through extensive behavioral testing, quantitative trait locus (QTL) mapping, whole-genome sequencing, and RNA sequencing, to uncover phenotypic and genotypic differences related to anxiety-related behavior. However, the effects of anxiolytic drugs on anxiety-related behavior in these strains have not been studied previously. This study allowed us to expand on previous findings to further characterize the anxiety-related behavior of these unique strains, using an anxiolytic drug. The goal of this study was to determine whether the treatment of adult male and female High Activity (low anxiety) and Low Activity (high anxiety) mice with diazepam, an agonist at the benzodiazepine allosteric site on the GABA
MeSH term(s)	Animals ; Diazepam/pharmacology ; Male ; Anti-Anxiety Agents/pharmacology ; Female ; Anxiety/drug therapy ; Mice ; Mice, Inbred Strains ; Disease Models, Animal ; Open Field Test/drug effects ; Species Specificity ; Behavior, Animal/drug effects
Chemical Substances	Diazepam (Q3JTX2Q7TU) ; Anti-Anxiety Agents
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2023.114343
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