دورية أكاديمية
أعرض في EDS

Testing Association of Previously Implicated Gene Sets and Gene-Networks in Nicotine Exposed Mouse Models with Human Smoking Phenotypes.

التفاصيل البيبلوغرافية
العنوان: Testing Association of Previously Implicated Gene Sets and Gene-Networks in Nicotine Exposed Mouse Models with Human Smoking Phenotypes.
المؤلفون: Mize TJ; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.; Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA., Funkhouser SA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA., Buck JM; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.; Department of Integrative Physiology, University of Colorado, Boulder, CO, USA., Stitzel JA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.; Department of Integrative Physiology, University of Colorado, Boulder, CO, USA., Ehringer MA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.; Department of Integrative Physiology, University of Colorado, Boulder, CO, USA., Evans LM; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.; Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA.
المصدر: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco [Nicotine Tob Res] 2023 Apr 06; Vol. 25 (5), pp. 1030-1038.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9815751 Publication Model: Print Cited Medium: Internet ISSN: 1469-994X (Electronic) Linking ISSN: 14622203 NLM ISO Abbreviation: Nicotine Tob Res Subsets: MEDLINE
أسماء مطبوعة: Publication: <2009->: Oxford : Oxford University Press
Original Publication: Abingdon, Oxfordshire, UK : Carfax Pub. and Society for Research on Nicotine and Tobacco, c1999-
مواضيع طبية MeSH: Nicotine* , Smoking*/genetics, Humans ; Animals ; Mice ; Phenotype ; Tobacco Smoking ; Disease Models, Animal
مستخلص: Introduction: Smoking behaviors are partly heritable, yet the genetic and environmental mechanisms underlying smoking phenotypes are not fully understood. Developmental nicotine exposure (DNE) is a significant risk factor for smoking and leads to gene expression changes in mouse models; however, it is unknown whether the same genes whose expression is impacted by DNE are also those underlying smoking genetic liability. We examined whether genes whose expression in D1-type striatal medium spiny neurons due to DNE in the mouse are also associated with human smoking behaviors.
Methods: Specifically, we assessed whether human orthologs of mouse-identified genes, either individually or as a set, were genetically associated with five human smoking traits using MAGMA and S-LDSC while implementing a novel expression-based gene-SNP annotation methodology.
Results: We found no strong evidence that these genes sets were more strongly associated with smoking behaviors than the rest of the genome, but ten of these individual genes were significantly associated with three of the five human smoking traits examined (p < 2.5e-6). Three of these genes have not been reported previously and were discovered only when implementing the expression-based annotation.
Conclusions: These results suggest the genes whose expression is impacted by DNE in mice are largely distinct from those contributing to smoking genetic liability in humans. However, examining a single mouse neuronal cell type may be too fine a resolution for comparison, suggesting that experimental manipulation of nicotine consumption, reward, or withdrawal in mice may better capture genes related to the complex genetics of human tobacco use.
Implications: Genes whose expression is impacted by DNE in mouse D1-type striatal medium spiny neurons were not found to be, as a whole, more strongly associated with human smoking behaviors than the rest of the genome, though ten individual mouse-identified genes were associated with human smoking traits. This suggests little overlap between the genetic mechanisms impacted by DNE and those influencing heritable liability to smoking phenotypes in humans. Further research is warranted to characterize how developmental nicotine exposure paradigms in mice can be translated to understand nicotine use in humans and their heritable effects on smoking.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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معلومات مُعتمدة: R01 DA044283 United States DA NIDA NIH HHS; R01 MH100141 United States MH NIMH NIH HHS; T32 DA017637 United States NH NIH HHS; R01 AG046938 United States AG NIA NIH HHS
المشرفين على المادة: 6M3C89ZY6R (Nicotine)
تواريخ الأحداث: Date Created: 20221129 Date Completed: 20230410 Latest Revision: 20231229
رمز التحديث: 20231229
مُعرف محوري في PubMed: PMC10077928
DOI: 10.1093/ntr/ntac269
PMID: 36444815
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-994X
DOI:10.1093/ntr/ntac269