Multi-omic and multi-species meta-analyses of nicotine consumption
Abstract Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a mod...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-02-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-021-01231-y |
| _version_ | 1818967585525334016 |
|---|---|
| author | Rohan H. C. Palmer Chelsie E. Benca-Bachman Spencer B. Huggett Jason A. Bubier John E. McGeary Nikhil Ramgiri Jenani Srijeyanthan Jingjing Yang Peter M. Visscher Jian Yang Valerie S. Knopik Elissa J. Chesler |
| author_facet | Rohan H. C. Palmer Chelsie E. Benca-Bachman Spencer B. Huggett Jason A. Bubier John E. McGeary Nikhil Ramgiri Jenani Srijeyanthan Jingjing Yang Peter M. Visscher Jian Yang Valerie S. Knopik Elissa J. Chesler |
| author_sort | Rohan H. C. Palmer |
| collection | DOAJ |
| description | Abstract Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a model organism geneset by collecting results from five animal models of nicotine exposure (RNA expression changes in brain) and then tested the relevance of these genes and flanking genetic variation using genetic data from human cigarettes per day (UK BioBank N = 123,844; all European Ancestry). We tested three hypotheses: (1) DNA variation in, or around, the ‘model organism geneset’ will contribute to the heritability to human tobacco consumption, (2) that the model organism genes will be enriched for genes associated with human tobacco consumption, and (3) that a polygenic score based off our model organism geneset will predict tobacco consumption in the AddHealth sample (N = 1667; all European Ancestry). Our results suggested that: (1) model organism genes accounted for ~5–36% of the observed SNP-heritability in human tobacco consumption (enrichment: 1.60–31.45), (2) model organism genes, but not negative control genes, were enriched for the gene-based associations (MAGMA, H-MAGMA, SMultiXcan) for human cigarettes per day, and (3) polygenic scores based on our model organism geneset predicted cigarettes per day in an independent sample. Altogether, these findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption. |
| first_indexed | 2024-12-20T13:51:08Z |
| format | Article |
| id | doaj.art-7eeffb2cb83f4b5981d84eb314c45aa0 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-20T13:51:08Z |
| publishDate | 2021-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-7eeffb2cb83f4b5981d84eb314c45aa02022-12-21T19:38:30ZengNature Publishing GroupTranslational Psychiatry2158-31882021-02-0111111010.1038/s41398-021-01231-yMulti-omic and multi-species meta-analyses of nicotine consumptionRohan H. C. Palmer0Chelsie E. Benca-Bachman1Spencer B. Huggett2Jason A. Bubier3John E. McGeary4Nikhil Ramgiri5Jenani Srijeyanthan6Jingjing Yang7Peter M. Visscher8Jian Yang9Valerie S. Knopik10Elissa J. Chesler11Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory UniversityBehavioral Genetics of Addiction Laboratory, Department of Psychology, Emory UniversityBehavioral Genetics of Addiction Laboratory, Department of Psychology, Emory UniversityThe Jackson LaboratoryDepartment of Psychiatry and Human Behavior, Brown UniversityBehavioral Genetics of Addiction Laboratory, Department of Psychology, Emory UniversityBehavioral Genetics of Addiction Laboratory, Department of Psychology, Emory UniversityDepartment of Human Genetics, Emory University School of MedicineInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandDepartment of Human Development and Family Studies, Purdue UniversityThe Jackson LaboratoryAbstract Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a model organism geneset by collecting results from five animal models of nicotine exposure (RNA expression changes in brain) and then tested the relevance of these genes and flanking genetic variation using genetic data from human cigarettes per day (UK BioBank N = 123,844; all European Ancestry). We tested three hypotheses: (1) DNA variation in, or around, the ‘model organism geneset’ will contribute to the heritability to human tobacco consumption, (2) that the model organism genes will be enriched for genes associated with human tobacco consumption, and (3) that a polygenic score based off our model organism geneset will predict tobacco consumption in the AddHealth sample (N = 1667; all European Ancestry). Our results suggested that: (1) model organism genes accounted for ~5–36% of the observed SNP-heritability in human tobacco consumption (enrichment: 1.60–31.45), (2) model organism genes, but not negative control genes, were enriched for the gene-based associations (MAGMA, H-MAGMA, SMultiXcan) for human cigarettes per day, and (3) polygenic scores based on our model organism geneset predicted cigarettes per day in an independent sample. Altogether, these findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption.https://doi.org/10.1038/s41398-021-01231-y |
| spellingShingle | Rohan H. C. Palmer Chelsie E. Benca-Bachman Spencer B. Huggett Jason A. Bubier John E. McGeary Nikhil Ramgiri Jenani Srijeyanthan Jingjing Yang Peter M. Visscher Jian Yang Valerie S. Knopik Elissa J. Chesler Multi-omic and multi-species meta-analyses of nicotine consumption Translational Psychiatry |
| title | Multi-omic and multi-species meta-analyses of nicotine consumption |
| title_full | Multi-omic and multi-species meta-analyses of nicotine consumption |
| title_fullStr | Multi-omic and multi-species meta-analyses of nicotine consumption |
| title_full_unstemmed | Multi-omic and multi-species meta-analyses of nicotine consumption |
| title_short | Multi-omic and multi-species meta-analyses of nicotine consumption |
| title_sort | multi omic and multi species meta analyses of nicotine consumption |
| url | https://doi.org/10.1038/s41398-021-01231-y |
| work_keys_str_mv | AT rohanhcpalmer multiomicandmultispeciesmetaanalysesofnicotineconsumption AT chelsieebencabachman multiomicandmultispeciesmetaanalysesofnicotineconsumption AT spencerbhuggett multiomicandmultispeciesmetaanalysesofnicotineconsumption AT jasonabubier multiomicandmultispeciesmetaanalysesofnicotineconsumption AT johnemcgeary multiomicandmultispeciesmetaanalysesofnicotineconsumption AT nikhilramgiri multiomicandmultispeciesmetaanalysesofnicotineconsumption AT jenanisrijeyanthan multiomicandmultispeciesmetaanalysesofnicotineconsumption AT jingjingyang multiomicandmultispeciesmetaanalysesofnicotineconsumption AT petermvisscher multiomicandmultispeciesmetaanalysesofnicotineconsumption AT jianyang multiomicandmultispeciesmetaanalysesofnicotineconsumption AT valeriesknopik multiomicandmultispeciesmetaanalysesofnicotineconsumption AT elissajchesler multiomicandmultispeciesmetaanalysesofnicotineconsumption |