Genetic and Epigenetic Foundations of Childhood Internalizing and Externalizing Problems and their Co-occurrence Article Swipe
Mona Bekkhus
,
Stella Tsotsi
,
Christian M. Page
,
Nikolai Olavi Czajkowski
,
Wanlin Liu
,
Espen Røysamb
,
Ragnhild Bang Nes
,
Aurora Oftedal
,
Robert Lyle
,
Laurie J. Hannigan
,
Ole A. Andreassen
,
Yunpeng Wang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.05.24.25328240
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.05.24.25328240
Childhood behavioural problems pose long-term mental health risks, yet the biological basis of co-occurring internalizing and externalizing symptoms remains unclear. In a cohort of 40,212 children, we integrated genome-wide association studies (GWAS), polygenic scores (PGS), and DNA methylation profiling (EWAS) to examine the genetic and epigenetic underpinnings of internalizing, externalizing, and co-occurring problems. All outcomes showed modest SNP-based heritability (h² = 0.02–0.19, FDR < 0.05). GWAS identified a significant locus for co-occurring problems at age five (rs73161798, p = 3.26 × 10⁻⁸), near USP12 , a gene implicated in neuroplasticity and risk-taking. PGS for co-occurring symptoms was associated with higher neuroticism and lower cognitive ability. DNA methylation explained substantial variance in co-occurring problems at ages three (R² = 0.19) and five (R² = 0.62), but not in single-domain symptoms. EWAS revealed 101 significant sites (p < 10⁻⁷) linked to neurodevelopmental, immune, and metabolic pathways. These findings suggest that co-occurring behavioural problems have a distinct, age-sensitive biological architecture.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.05.24.25328240
- https://www.medrxiv.org/content/medrxiv/early/2025/05/25/2025.05.24.25328240.full.pdf
- OA Status
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- Cited By
- 1
- References
- 69
- Related Works
- 10
- OpenAlex ID
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Raw OpenAlex JSON
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https://openalex.org/W4410719103Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.05.24.25328240Digital Object Identifier
- Title
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Genetic and Epigenetic Foundations of Childhood Internalizing and Externalizing Problems and their Co-occurrenceWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-05-25Full publication date if available
- Authors
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Mona Bekkhus, Stella Tsotsi, Christian M. Page, Nikolai Olavi Czajkowski, Wanlin Liu, Espen Røysamb, Ragnhild Bang Nes, Aurora Oftedal, Robert Lyle, Laurie J. Hannigan, Ole A. Andreassen, Yunpeng WangList of authors in order
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https://doi.org/10.1101/2025.05.24.25328240Publisher landing page
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https://www.medrxiv.org/content/medrxiv/early/2025/05/25/2025.05.24.25328240.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.medrxiv.org/content/medrxiv/early/2025/05/25/2025.05.24.25328240.full.pdfDirect OA link when available
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Epigenetics, Psychology, Co-occurrence, Developmental psychology, Genetics, Biology, Computer science, Gene, Artificial intelligenceTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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69Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(PGS), | 35 |
| abstract_inverted_index.0.05). | 65 |
| abstract_inverted_index.0.62), | 124 |
| abstract_inverted_index.40,212 | 25 |
| abstract_inverted_index.cohort | 23 |
| abstract_inverted_index.health | 7 |
| abstract_inverted_index.higher | 100 |
| abstract_inverted_index.linked | 138 |
| abstract_inverted_index.mental | 6 |
| abstract_inverted_index.modest | 57 |
| abstract_inverted_index.risks, | 8 |
| abstract_inverted_index.scores | 34 |
| abstract_inverted_index.showed | 56 |
| abstract_inverted_index.(GWAS), | 32 |
| abstract_inverted_index.examine | 42 |
| abstract_inverted_index.genetic | 44 |
| abstract_inverted_index.immune, | 141 |
| abstract_inverted_index.remains | 19 |
| abstract_inverted_index.studies | 31 |
| abstract_inverted_index.suggest | 147 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.ability. | 105 |
| abstract_inverted_index.findings | 146 |
| abstract_inverted_index.outcomes | 55 |
| abstract_inverted_index.problems | 3, 73, 113, 151 |
| abstract_inverted_index.revealed | 131 |
| abstract_inverted_index.symptoms | 18, 96 |
| abstract_inverted_index.unclear. | 20 |
| abstract_inverted_index.variance | 110 |
| abstract_inverted_index.10⁻⁷) | 137 |
| abstract_inverted_index.Childhood | 1 |
| abstract_inverted_index.SNP-based | 58 |
| abstract_inverted_index.children, | 26 |
| abstract_inverted_index.cognitive | 104 |
| abstract_inverted_index.distinct, | 154 |
| abstract_inverted_index.explained | 108 |
| abstract_inverted_index.long-term | 5 |
| abstract_inverted_index.metabolic | 143 |
| abstract_inverted_index.pathways. | 144 |
| abstract_inverted_index.polygenic | 33 |
| abstract_inverted_index.problems. | 53 |
| abstract_inverted_index.profiling | 39 |
| abstract_inverted_index.symptoms. | 129 |
| abstract_inverted_index.10⁻⁸), | 82 |
| abstract_inverted_index.associated | 98 |
| abstract_inverted_index.biological | 11, 156 |
| abstract_inverted_index.epigenetic | 46 |
| abstract_inverted_index.identified | 67 |
| abstract_inverted_index.implicated | 88 |
| abstract_inverted_index.integrated | 28 |
| abstract_inverted_index.association | 30 |
| abstract_inverted_index.behavioural | 2, 150 |
| abstract_inverted_index.genome-wide | 29 |
| abstract_inverted_index.methylation | 38, 107 |
| abstract_inverted_index.neuroticism | 101 |
| abstract_inverted_index.significant | 69, 133 |
| abstract_inverted_index.substantial | 109 |
| abstract_inverted_index.(rs73161798, | 77 |
| abstract_inverted_index.0.02–0.19, | 62 |
| abstract_inverted_index.co-occurring | 14, 52, 72, 95, 112, 149 |
| abstract_inverted_index.heritability | 59 |
| abstract_inverted_index.risk-taking. | 92 |
| abstract_inverted_index.age-sensitive | 155 |
| abstract_inverted_index.architecture. | 157 |
| abstract_inverted_index.externalizing | 17 |
| abstract_inverted_index.internalizing | 15 |
| abstract_inverted_index.single-domain | 128 |
| abstract_inverted_index.underpinnings | 47 |
| abstract_inverted_index.externalizing, | 50 |
| abstract_inverted_index.internalizing, | 49 |
| abstract_inverted_index.neuroplasticity | 90 |
| abstract_inverted_index.neurodevelopmental, | 140 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| countries_distinct_count | 0 |
| institutions_distinct_count | 12 |
| citation_normalized_percentile.value | 0.92871306 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |