Atad1 Is a Potential Candidate Gene for Prepulse Inhibition
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Acoustic Startle and Prepulse Inhibition
2.3. Single-Trait Mapping for Behavioral QTLs
2.4. Criteria for Identification of Candidate Genes
2.5. Gene Expression Datasets
2.6. Functional Analysis
2.7. Correlation and PheWAS Analyses
2.8. Protein–Protein Interaction Network Analysis
2.9. Validation of Candidate Genes Using Human RNA Sequencing Data
3. Results
3.1. Prepulse Inhibition
3.2. Identification of Candidate Genes
3.3. Genetic, Partial, and Literature Correlations for Identified Candidate and Gene Sets
3.4. Gene Enrichment Analysis
3.5. Phenotype Correlation
3.6. Protein–Protein Interaction Network
3.7. PheWAS Analysis
3.8. Candidate Variants in Atad1
3.9. Validation of the Candidate Gene in Schizophrenia Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PPI | Prepulse Inhibition |
QTL | Quantitative Trait Locus |
BXD RI | B6 × D2 Recombinant Inbred Strain |
B6 | C57/BL6 |
D2 | DBA2/J |
PheWAS | Phenome-Wide Association Study |
GN | GeneNetwork |
LRS | Likelihood Ratio Statistic |
Atad1 | ATPase family, AAA domain containing 1, also known as thorase |
PFC | Prefrontal Cortex |
HIPP | Hippocampus |
STR | Striatum |
NAc | Nucleus Accumbens |
MDB | Midbrain |
VTA | Ventral Tegmental Area |
AMYG | Amygdala |
HYPO | Hypothalamus |
GRIA2 | Glutamate Ionotropic Receptor AMPA type 2 subunit |
ASNA1 | Arsenical Pump-Driving ATPase 1 |
GWAS | Genome-Wide Association Study |
Disc1 | Disrupted in Schizophrenia 1 |
Nrg1 | Neuregulin 1 |
Chr | Chromosome |
SNP | Single-Nucleotide Polymorphism |
GEMMA | Genome-Wide Efficient Mixed-Model Analysis |
LOD | Logarithm Odds |
MGI | Mouse Genome Informatics |
RGD | Rat Genome Database |
IMPC | International Mouse Phenotyping Consortium |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
mRNA | Messenger RNA |
RMA | Robust Multi-Array Average |
STRING | Search Tool for the Retrieval of Interacting Genes/Proteins |
GEO | Gene Expression Omnibus |
Prkg1 | Protein Kinase cGMP-dependent type 1 |
Rnls | Renalase, FAD Dependent Amine Oxidase |
Asah2 | N-acylsphingosine amidohydrolase 2 |
Papss2 | 3′-phosphoadenosine 5′ phosphosulfate synthase 2 |
Ifit1 | Interferon-induced protein with tetratricopeptide repeats 1 |
Cdc37l1 | Cell Division cycle 37 homolog-like 1 |
Ak3 | Adenylate Kinase 3 |
Ranbp6 | RAN binding protein 6 |
Ifit1bl2 | Interferon-induced protein with tetratricopeptide repeats 1B like 2 |
MPO | Mammalian Phenotype Ontology |
GO-BP | Gene Ontology Biological Processes |
HPO | Human Phenotype Ontology |
FDR | False Discovery Rate |
ND | Node Degree |
EED | Embryonic Ectoderm Development |
TIA1 | Cytotoxic Granule-Associated RNA binding protein 1 |
RGS14 | Regulator of G protein Signaling 14 |
DLG4 | Discs Large Homolog 4 |
ZBTB7B | Zinc finger and BTB domain containing 7B |
GRIA2 | Glutamate Ionotropic Receptor AMPA type subunit 2 |
bp | Base pair |
UTR | Untranslated Region |
PCA | Principal Component Analysis |
Fabp7 | Fatty acid binding protein 7 |
Ptpn5 | Tyrosine-Protein-Phosphatase Non-receptor Type 5 |
APBB1lP | Amyloid Beta Precursor Protein Binding Family B Member 1 Interacting Protein |
AMPAR | AMPA receptor |
LTD | Long-Term Depression |
cKO | Conditional Knockout |
GRIP1 | AMPAR/Glutamate Interacting-Protein 1 |
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Official Symbol | Mean Expression ≥ 8 (Score = 1) | Non-Syn SNPs/Indels (Score = 2) | Cis-Regulation (Score = 2) | Sig. Phenotype Correlation (Score = 2) | Functional Significance (Score = 3) | Total (Score = 10) |
---|---|---|---|---|---|---|
Atad1 | Yes | Yes | Yes | Yes | Yes | 10 |
Rnls | -- | Yes | Yes | Yes | Yes | 9 |
Prkg1 | Yes | Yes | -- | Yes | Yes | 8 |
Asah2 | -- | Yes | -- | Yes | Yes | 7 |
Ifit1 | -- | Yes | -- | Yes | Yes | 7 |
Cdc3711 | Yes | -- | -- | Yes | Yes | 6 |
Ak3 | Yes | -- | -- | Yes | Yes | 6 |
Papps2 | Yes | -- | Yes | Yes | -- | 5 |
Ifit1bl2 | -- | -- | -- | Yes | Yes | 5 |
Ranbp6 | Yes | -- | -- | Yes | -- | 3 |
Atlas ID | PMID | Year | Trait | p-Value | N |
---|---|---|---|---|---|
12 | 24280982 | 2014 | Schizophrenia/bipolar disorder | 0.040 | 39,202 |
15 | 28439101 | 2017 | Post-traumatic stress disorder | 0.013 | 9223 |
30 | 21173776 | 2012 | Agreeableness (NEO-FFI) | 0.047 | 17,375 |
1141 | 27494321 | 2016 | Chronotype | 0.001 | 128,266 |
1142 | 27494321 | 2016 | Sleep duration | 0.045 | 128,266 |
1173 | 26955885 | 2016 | Chronotype (continuous) | 4.98 × 10−5 | 100,420 |
1174 | 26955885 | 2016 | Extreme chronotype | 0.032 | 100,420 |
2018 | 24369049 | 2014 | Lithium response in Bipolar I patients—Alda Scale of 7 to 8 | 0.042 | 294 |
2025 | 22952603 | 2012 | 10 mg response to amphetamine | 0.025 | 381 |
2043 | 27329760 | 2016 | Bipolar disorder | 0.036 | 34,950 |
3230 | 31427789 | 2019 | Morning/evening person (chronotype) | 0.040 | 345,148 |
3235 | 31427789 | 2019 | Current tobacco smoking | 0.009 | 386,150 |
3262 | 31427789 | 2019 | Average weekly red wine intake | 0.025 | 274,058 |
3287 | 31427789 | 2019 | Sensitivity/hurt feelings | 0.042 | 375,272 |
3292 | 31427789 | 2019 | Worry too long after embarrassment | 0.002 | 370,660 |
3295 | 31427789 | 2019 | Guilty feelings | 0.000 | 376,361 |
3296 | 31427789 | 2019 | Risk-taking | 0.031 | 372,651 |
3297 | 31427789 | 2019 | Frequency of depressed mood in last 2 weeks | 0.001 | 370,017 |
3394 | 31427789 | 2019 | Ever unenthusiastic/disinterested for a whole week | 0.024 | 123,848 |
3567 | 31427789 | 2019 | Why stopped smoking: illness or ill health | 0.021 | 94,509 |
3655 | 31427789 | 2019 | Smoking status: previous vs. current | 0.014 | 177,025 |
3729 | 31427789 | 2019 | Depression—age at first episode of depression | 0.009 | 65,776 |
3744 | 31427789 | 2019 | Cannabis use—ever taken cannabis | 0.012 | 126,632 |
3770 | 31427789 | 2019 | Depression—trouble falling or staying asleep or sleeping too much | 0.001 | 126,545 |
3772 | 31427789 | 2019 | Depression—recent feelings of tiredness or low energy | 0.030 | 126,540 |
3775 | 31427789 | 2019 | Traumatic events—able to pay rent/mortgage as an adult | 0.014 | 124,944 |
3795 | 29942085 | 2018 | Neuroticism | 0.015 | 390,278 |
3796 | 29942085 | 2018 | Depressive symptoms | 0.011 | 381,455 |
3982 | 29483656 | 2018 | Schizophrenia | 0.002 | 105,318 |
3993 | 29500382 | 2018 | Irritability (IRR) | 0.048 | 260,369 |
3999 | 29500382 | 2018 | Worry too long after embarrassment (WORR-EMB) | 0.001 | 261,094 |
4002 | 29500382 | 2018 | Guilty feelings (GUILT) | 0.001 | 265,139 |
4014 | 29700475 | 2018 | Major depressive disorder | 0.004 | 173,005 |
4040 | 29906448 | 2018 | Schizophrenia/bipolar disorder | 0.037 | 107,620 |
4087 | 29255261 | 2018 | Neuroticism | 0.010 | 329,821 |
4294 | 30696823 | 2019 | Chronotype | 0.029 | 449,732 |
4316 | 30643251 | 2019 | Smoking cessation | 0.005 | 312,821 |
4368 | 30150663 | 2018 | Cannabis use | 0.013 | 162,082 |
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Bajpai, A.K.; Freels, T.G.; Lu, L.; Cook, M.N. Atad1 Is a Potential Candidate Gene for Prepulse Inhibition. Genes 2025, 16, 1139. https://doi.org/10.3390/genes16101139
Bajpai AK, Freels TG, Lu L, Cook MN. Atad1 Is a Potential Candidate Gene for Prepulse Inhibition. Genes. 2025; 16(10):1139. https://doi.org/10.3390/genes16101139
Chicago/Turabian StyleBajpai, Akhilesh K., Timothy G. Freels, Lu Lu, and Melloni N. Cook. 2025. "Atad1 Is a Potential Candidate Gene for Prepulse Inhibition" Genes 16, no. 10: 1139. https://doi.org/10.3390/genes16101139
APA StyleBajpai, A. K., Freels, T. G., Lu, L., & Cook, M. N. (2025). Atad1 Is a Potential Candidate Gene for Prepulse Inhibition. Genes, 16(10), 1139. https://doi.org/10.3390/genes16101139