Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis
Abstract
:1. Introduction
2. Results
2.1. Sample Description
2.2. Epigenetic Age
2.3. Epigenome-Wide Association Study
2.4. Methylation Risk Score
3. Discussion
3.1. Years of Schooling Was Associated with Epigenetic Age in EOP
3.2. EWAS Suggested Potential Novel Associations with EOP
3.3. Association Between Clinical Characteristics Associated with Psychosis MRS
3.4. Limitations
4. Materials and Methods
4.1. Sample Population
4.2. Study Design
4.3. DNA Extraction
4.4. Genomic-Wide Quantification of DNA Methylation
4.5. Epigenetic Clocks
4.6. Statistical Analysis
4.7. EWAS and Methylation Risk Score
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADGRV1 | Adhesion G Protein-Coupled Receptor V1 gene |
BLUP | Best Linear Unbiased Prediction |
CEP164 | Centrosomal Protein 164 gene |
CpG | Cytosine–guanine site |
DNA | Deoxyribonucleic acid |
DNAm | Deoxyribonucleic acid methylation |
DNAmTL | DNA methylation-based telomere length |
DSM-5 | Diagnostic and Statistical Manual of Mental Disorders, 5th Edition |
DunedinPoAm38 | Dunedin Pace of Aging |
EN | Elastic Net |
EOP | Early-onset psychosis |
EOP-MRS | Psychosis methylation risk score |
EWAS | Epigenome-wide association study |
FEP | First episode of psychosis |
GAF | Global assessment of functioning |
HIST1H2BB | Histone Cluster 1 H2B Family Member B gene |
IRF2BP1 | Interferon Regulatory Factor 2 Binding Protein 1 gene |
K-SADS PL-5 | Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime version DSM-5 |
MAP1B | Microtubule-Associated Protein 1B gene |
MRS | Methylation risk score |
NAALAD2 | N-Acetylated α-Linked Acidic Dipeptidase 2 gene |
PC | Principal component |
PedBE | Pediatric Buccal Epigenetic |
SULT1C4 | Sulfotransferase Family 1C Member 4 gene |
TSS | Transcription start site |
VIF | Variance inflation factor |
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Characteristic | EOP (n = 12) | Non-EOP (n = 11) | p | |
---|---|---|---|---|
Age | years ± SD | 15.5 ± 1.56 | 13.36 ± 2.57 | 0.030 a |
Gender | Male, n (%) | 6 (50) | 7 (64) | 0.680 c |
Female, n (%) | 6 (50) | 4 (36) | ||
Education | years ± SD | 9.3 ± 1.96 | 7.2 ± 2.05 | 0.023 a |
Body mass index | z-score, mean ± SD | 1.08 ± 1.15 | 0.67 ± 1.50 | 0.368 a |
Psychiatric admissions | n (%) | 7 (58) | 1 (9) | 0.027 c |
Total, median (min–max) | 1 (0–4) | 0 (0–1) | 0.016 b | |
Psychiatric comorbidity | n (%) | 12(100) | 9 (81) | 0.370 c |
Mood disorders, n (%) | 11 (91) | 8 (72) | 0.316 c | |
Anxiety and stress disorders, n (%) | 10 (83) | 4 (36) | 0.036 c | |
Conduct disorders, n (%) | 5 (41) | 5 (45) | 1 c | |
Neurodevelopment disorders, n (%) | 1 (8) | 4 (36) | 0.155 c | |
Eating disorder, n (%) | 4 (33) | 0 | 0.093 c | |
GAF | Total score, mean ± SD | 43.33 ± 15.14 | 74 ± 6.41 | 0.00003 a |
Minimal, n (%) | 1 (8) | 3 (27) | 0.017 c | |
Mild, n (%) | 1 (8) | 2 (18) | ||
Moderate, n (%) | 2 (16) | 0 | ||
Severe, n (%) | 8 (66) | 0 | ||
Epigenetic age | Wu’s clock, mean ± SD | 11.08 ± 0.89 | 10.29 ± 0.78 | 0.015 |
Epigenetic Calculator | Age r, p | GAF r, p | Admissions r, p |
---|---|---|---|
BLUP | 0.37, 0.079 | −0.40, 0.056 | 0.40, 0.056 |
DNAmTL | −0.12, 0.555 | 0.27, 0.198 | −0.43, 0.038 |
DunnedinPoAm38 | 0.26, 0.224 | −0.17, 0.434 | 0.19, 0.368 |
EN | 0.26, 0.220 | −0.26, 0.217 | 0.40, 0.057 |
Hannum | 0.25, 0.238 | −0.23, 0.274 | 0.29, 0.174 |
Horvath-1 | 0.18, 0.398 | 0.13, 0.553 | −0.07, 0.742 |
Horvath-2 | 0.03, 0.848 | −0.17, 0.427 | 0.34, 0.107 |
Levine | 0.35, 0.100 | −0.05, 0.806 | 0.09, 0.672 |
PedBE | 0.41, 0.046 | −0.53, 0.008 | 0.56, 0.005 |
Wu | 0.30, 0.150 | −0.45, 0.027 | 0.49, 0.015 |
Zhang | 0.24, 0.253 | −0.21, 0.324 | 0.35, 0.097 |
Epiclock | Age (Years) | Sex | Schooling (Years) | Comorbidity | Admissions | |||||
---|---|---|---|---|---|---|---|---|---|---|
β, SE (CI 95) | p | β, SE (CI 95) | p | β, SE (CI 95) | p | β, SE (CI 95) | p | β, SE (CI 95) | p | |
BLUP | 1.78, 0.55 (0.62, 2.94) | 0.004 | - | - | −1.82, 0.54 (−2.96, −0.67) | 0.003 | 0.49, 0.22 (0.02, 0.97) | 0.041 | - | - |
DNAmTL | −0.07, 0.02 (−0.11, −0.02) | 0.006 | - | - | 0.08, 0.02 (0.03, 0.13) | 0.001 | - | - | −0.13, 0.05 (−0.24, −0.02) | 0.017 |
EN | 1.36, 0.58 (0.12, 2.60) | 0.032 | - | - | −1.47, 0.58 (−2.69, −0.25) | 0.020 | - | - | - | - |
Horvath-1 | 1.75, 0.70 (0.26, 3.24) | 0.023 | - | - | - | - | - | - | - | - |
Horvath-2 | 0.60, 0.26 (0.04, 1.16) | 0.034 | - | - | −0.90, 0.26 (−1.45, −0.35) | 0.002 | 0.31, 0.10 (0.08, 2.38) | 0.010 | - | - |
Levine | 5.07, 1.10 (2.74, 7.40) | 0.001 | 8.41, 2.37 (3.4, 13.40) | 0.002 | −5.01, 1.20 (−7.55, −2.48) | 0.001 | - | - | - | - |
PedBE | 0.35, 0.10 (0.13, 0.58) | 0.003 | - | - | −0.31, 0.10 (−0.53, −0.09) | 0.008 | - | - | - | - |
Wu | - | - | - | - | - | - | - | - | 0.81, 0.37 (0.03, 1.60) | 0.042 |
Zhang | 1.93, 0.66 (0.56, 3.31) | 0.008 | - | - | −1.81, 0.69 (−3.25, −0.36) | 0.016 | - | - | - | - |
CpG | Gene Annotation | Chr | Position | Relation to Island | β | SE | T | p |
---|---|---|---|---|---|---|---|---|
cg24772138 | MAP1B (Body) | 5 | 71,405,539 | S Shore | −0.4483 | 0.0508 | −8.8233 | 4.30 × 10−7 |
cg26028573 | HIST1H2BB (Exon) | 6 | 26,043,587 | N Shore | 0.2340 | 0.0264 | 8.8374 | 4.22 × 10−7 |
cg05100917 | CEP164 (TSS200) | 11 | 117,198,460 | Island | −0.5790 | 0.0627 | −9.2343 | 2.48 × 10−7 |
cg20150189 | SULT1C4 (Body) | 2 | 108,999,219 | Open Sea | −0.3525 | 0.0498 | −7.0718 | 5.58 × 10−6 |
cg27181762 | ADGRV1 (Body) | 5 | 90,195,345 | Open Sea | −0.5829 | 0.0860 | −6.7701 | 9.02 × 10−6 |
cg13883911 | - | 8 | 33,430,120 | Open Sea | 0.3104 | 0.0449 | 6.9051 | 7.26 × 10−6 |
cg08523325 | NAALAD2 (Body) | 11 | 89,901,450 | Open Sea | −0.3064 | 0.0448 | −6.8337 | 8.14 × 10−6 |
cg06583549 | IRF2BP1 (Exon) | 19 | 46,387,962 | Island | −0.2669 | 0.0350 | −7.6212 | 2.40 × 10−6 |
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Ruiz-Ramos, D.; Martínez-Magaña, J.J.; Juárez-Rojop, I.E.; Nolasco-Rosales, G.A.; Sosa-Hernández, F.; Cruz-Castillo, J.D.; Cavazos, J.; Callejas, A.; Zavaleta-Ramírez, P.; Zorrilla-Dosal, J.A.; et al. Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis. Genes 2025, 16, 591. https://doi.org/10.3390/genes16050591
Ruiz-Ramos D, Martínez-Magaña JJ, Juárez-Rojop IE, Nolasco-Rosales GA, Sosa-Hernández F, Cruz-Castillo JD, Cavazos J, Callejas A, Zavaleta-Ramírez P, Zorrilla-Dosal JA, et al. Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis. Genes. 2025; 16(5):591. https://doi.org/10.3390/genes16050591
Chicago/Turabian StyleRuiz-Ramos, David, José Jaime Martínez-Magaña, Isela Esther Juárez-Rojop, Germán Alberto Nolasco-Rosales, Fernanda Sosa-Hernández, Juan Daniel Cruz-Castillo, Josefa Cavazos, Adriana Callejas, Patricia Zavaleta-Ramírez, José Antonio Zorrilla-Dosal, and et al. 2025. "Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis" Genes 16, no. 5: 591. https://doi.org/10.3390/genes16050591
APA StyleRuiz-Ramos, D., Martínez-Magaña, J. J., Juárez-Rojop, I. E., Nolasco-Rosales, G. A., Sosa-Hernández, F., Cruz-Castillo, J. D., Cavazos, J., Callejas, A., Zavaleta-Ramírez, P., Zorrilla-Dosal, J. A., Lanzagorta, N., Nicolini, H., Montalvo-Ortiz, J. L., Glahn, D. C., & Genis-Mendoza, A. D. (2025). Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis. Genes, 16(5), 591. https://doi.org/10.3390/genes16050591