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ArticleScientific reports2025

Paternal valproate use and impact of shared genetic susceptibility on child neurodevelopment.

Emilie Willoch Olstad, Hedvig Marie Egeland Nordeng, Marte-Helene Bjørk, Kaja Selmer, Kristina Gervin

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Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Emilie Willoch OlstadPharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Hedvig Marie Egeland NordengPharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Marte-Helene BjørkDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Kaja SelmerDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
Kristina GervinUiO:RealArt Convergence Environment, University of Oslo, Oslo, Norway. Kristina.gervin@farmasi.uio.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paternal use of valproate during spermatogenesis has been associated with increased risk of neurodevelopmental disorders (NDDs) in offspring, yet the role of genetic confounding is unclear. Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa), we assessed genetic susceptibility to epilepsy, ADHD and autism spectrum disorders (ASD) in fathers with epilepsy treated with valproate (n = 41), lamotrigine or levetiracetam (n = 37), other anti-seizure medications (ASMs; n = 80), and healthy controls (n = 54,752). Fathers using valproate had significantly higher polygenic risk scores (PRSs) for epilepsy compared to those using lamotrigine or levetiracetam (mean difference: 0.66, 95% CI: 0.21-1.11, p ≈ 0.005), other ASMs (0.41, 95% CI: 0.02-0.81, p ≈ 0.04) and controls (0.85, 95% CI: 0.54-1.15, p = 5.8 × 10⁻⁸). No robust associations were found between paternal ASM use or epilepsy PRS and child neurodevelopmental outcomes. Significant genetic overlap was found among the top 1% of weighted SNPs in the PRSs for epilepsy, ADHD and ASD (428 genes, p ≈ 0.0001), enriched for neurodevelopmental pathways. These results emphasize the importance of considering shared genetic susceptibility when assessing risks of paternal valproate exposure.

Indexed as

AnticonvulsantsEpilepsyGenetic Predisposition to DiseaseNeurodevelopmental DisordersPaternal ExposureValproic AcidAdultAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderCase-Control StudiesChildChild, PreschoolFathersFemaleHumansLamotrigineAnticonvulsantsLamotrigineLevetiracetamValproic Acid

Identifiers

PMID41203668
PMCPMC12595016

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