New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork
Abstract
:1. Introduction
2. Materials and Methods
2.1. Phenotype Data
2.2. New Genotypes from Sequencing
2.3. Genome-Wide Efficient Mixed Model Association (GEMMA), Kinship within the BXD Strains, and QTL Mapping
2.4. Identification of Novel QTLs
2.5. QTL Confidence Intervals
2.6. Cis-eQTL Mapping
2.7. “Gene Friends”, or Co-Expression Analysis
2.8. Gene Variant Analysis
2.9. PheWAS
3. Results
3.1. Identification of QTLs
3.2. Novel QTL
3.3. Candidate Causal Genes within Novel QTL
3.4. Co-Expression Networks or “Gene-Friends”
3.5. Gene Variant Analysis
3.6. PheWAS Analysis of the Genes within QTLs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chromosome | QTL Confidence Interval (Mb) | Summary of Phenotype | Relevant Behaviour Phenotype | PMID of Relevant Phenotype |
---|---|---|---|---|
Chr1 | 37.671–78.94 | Locomotion | Loss of righting induced by ethanol | 8974320 |
Chr1 | 37.671–78.94 | Locomotion | Vertical clinging | 10086232 |
Chr1 | 68.798–80.329 | Cocaine and locomotion | Loss of righting induced by ethanol | 16803863 |
Chr1 | 91.214–99.884 | Vertical activity | Loss of righting induced by ethanol | 16803863 |
Chr3 | 51.723–56.473 | Vertical activity | ||
Chr7 | 97.466–104.149 | |||
Chr12 | 82.859–96.105 | BXD_11407 | ||
Chr14 | 109.994–114.751 | BXD_12023 | ||
Chr15 | 71.035–77.148 | Motor coordination, anxiety | Abnormal fear/anxiety-related behaviour | 10556431 |
Number of Variants | Type of Variant | Gene |
---|---|---|
2 | Missense | Ccdc169 |
1 | Missense | Ccna1 |
1 | In-frame insertion | Dclk1 |
2 | Frameshift | Frem2 |
1 | Stop loss | Frem2 |
9 | Missense | Frem2 |
1 | Frameshift | Mab21l1 |
6 | Missense | Mab21l1 |
9 | Frameshift | Nbea |
2 | In-frame deletions | Nbea |
19 | Missense | Nbea |
3 | Stop loss | Nbea |
4 | In-frame deletions | Postn |
1 | In-frame insertions | Postn |
6 | Missense | Postn |
1 | Start loss | Postn |
1 | Frameshift | Spg20 |
8 | Missense | Spg20 |
1 | Stop gain | Spg20 |
1 | Stop loss | Spg20 |
1 | Missense | Trpc4 |
Number of Variants | Type of Variant | Gene |
---|---|---|
3 | Frameshift | Cops4 |
3 | Missense | Cops4 |
1 | Missense | Enoph1 |
1 | Stop gain | Enoph1 |
1 | Frameshift | Hnrnpd |
5 | Missense | Hnrnpd |
3 | Missense | Hnrnpd |
1 | Splice donor | Hnrnpd |
2 | Frameshift | Hpse |
1 | In-frame insertion | Hpse |
13 | Missense | Hpse |
1 | Splice donor | Hpse |
3 | Missense | Lin54 |
1 | Frameshift | Sec31a |
1 | In-frame deletion | Sec31a |
1 | Splice donor | Sec31a |
1 | Missense | Tmem150c |
1 | Splice donor | Tmem150c |
Number of Variants | Type of Variant | Gene |
---|---|---|
1 | Frameshift | 4931429L15Ri |
2 | Missense | 4931429L15Ri |
1 | Stop gain | 4931429L15Ri |
2 | Frameshift | Cadm1 |
5 | Missense | Cadm1 |
1 | In-frame deletion | Cep164 |
3 | Missense | Cep164 |
1 | Stop loss | Cep164 |
atlas ID | PMID | Year | Domain | Trait | p-Value | N |
---|---|---|---|---|---|---|
4314 | 30643251 | 2019 | Psychiatric | Ever smoked regulary | 3.47 × 10−15 | 262990 |
3654 | 31427789 | 2019 | Psychiatric | Smoking status: Never | 2.45 × 10−12 | 384964 |
4327 | 30643256 | 2019 | Psychiatric | Well-being spectrum | 2.73 × 10−10 | 2311184 |
4322 | 30643256 | 2019 | Psychiatric | Depressive symptoms (univariate) | 3.58 × 10−10 | 1067913 |
4313 | 30643251 | 2019 | Psychiatric | Age of initiation of regular smoking | 1.16 × 10−8 | 632802 |
3425 | 31427789 | 2019 | Psychiatric | Ever smoked | 9.55 × 10−8 | 385013 |
3236 | 31427789 | 2019 | Psychiatric | Past tobacco smoking | 1.02 × 10−7 | 355594 |
4274 | 30846698 | 2019 | Psychiatric | Short sleep | 2.64 × 10−7 | 411934 |
3261 | 31427789 | 2019 | Psychiatric | Alcohol intake frequency | 3.80 × 10−7 | 386082 |
4326 | 30643256 | 2019 | Psychiatric | Depressive symptoms (MA GWAMA) | 5.12 × 10−7 | 1067913 |
56 | 27089181 | 2016 | Psychiatric | Depressive symptoms | 1.72 × 10−6 | 161460 |
3796 | 29942085 | 2018 | Psychiatric | Depressive symptoms | 1.75 × 10−6 | 381455 |
3235 | 31427789 | 2019 | Psychiatric | Current tobacco smoking | 2.71 × 10−6 | 386150 |
4293 | 30718901 | 2019 | Psychiatric | Depression | 3.19 × 10−6 | 500199 |
3268 | 31427789 | 2019 | Psychiatric | Alcohol intake versus 10 years previously | 3.41 × 10−6 | 357907 |
4171 | 29970889 | 2018 | Psychiatric | Loneliness | 3.44 × 10−6 | 445024 |
4170 | 29970889 | 2018 | Psychiatric | Loneliness (MTAG) | 3.72 × 10−6 | 487647 |
atlas ID | PMID | Year | Domain | Trait | p-Value | N |
---|---|---|---|---|---|---|
4327 | 30643256 | 2019 | Psychiatric | Well-being spectrum | 1.40 × 10−5 | 2311184 |
3998 | 29500382 | 2018 | Psychiatric | Tense | 1.23 × 10−5 | 263635 |
3291 | 31427789 | 2019 | Psychiatric | Tense | 2.80 × 10−4 | 374129 |
4293 | 30718901 | 2019 | Psychiatric | Depression | 3.12 × 10−4 | 500199 |
4325 | 30643256 | 2019 | Psychiatric | Neuroticism (MA GWAMA) | 3.94 × 10−4 | 523783 |
3798 | 29942085 | 2018 | Psychiatric | Worry subcluster | 5.57 × 10−4 | 348219 |
4087 | 29255261 | 2018 | Psychiatric | Neuroticism | 8.90 × 10−4 | 329821 |
4322 | 30643256 | 2019 | Psychiatric | Depressive symptoms (univariate) | 1.05 × 10−3 | 1067913 |
3301 | 31427789 | 2019 | Psychiatric | Seen doctor (GP) for nerves, anxiety, tension or depression | 1.11 × 10−3 | 383771 |
4321 | 30643256 | 2019 | Psychiatric | Neuroticism (univariate) | 1.12 × 10−3 | 523783 |
4326 | 30643256 | 2019 | Psychiatric | Depressive symptoms (MA GWAMA) | 1.27 × 10−3 | 1067913 |
3302 | 31427789 | 2019 | Psychiatric | Seen a psychiatrist for nerves, anxiety, tension or depression | 2.48 × 10−3 | 384700 |
3745 | 31427789 | 2019 | Psychiatric | Happiness and subjective well-being—General happiness | 2.83 × 10−3 | 126132 |
4011 | 29662059 | 2018 | Psychiatric | Broad depression | 3.34 × 10−3 | 322580 |
4013 | 29662059 | 2018 | Psychiatric | Major depressive disorder (ICD-coded) | 3.46 × 10−3 | 217584 |
4269 | 30867560 | 2019 | Psychiatric | Neuroticism general factor | 3.84 × 10−3 | 270059 |
3230 | 31427789 | 2019 | Psychiatric | Morning/evening person (chronotype) | 4.42 × 10−3 | 345148 |
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Chunduri, A.; Watson, P.M.; Ashbrook, D.G. New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork. Genes 2022, 13, 614. https://doi.org/10.3390/genes13040614
Chunduri A, Watson PM, Ashbrook DG. New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork. Genes. 2022; 13(4):614. https://doi.org/10.3390/genes13040614
Chicago/Turabian StyleChunduri, Alisha, Pamela M. Watson, and David G. Ashbrook. 2022. "New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork" Genes 13, no. 4: 614. https://doi.org/10.3390/genes13040614