Evidence map›Paper›PMID 41935183›Full record

ArticleMolecular psychiatry2026

Assessing molecular gene by treatment interactions using a population of neural progenitors exposed to valproic acid and lithium.

Jordan M Valone, Brandon D Le, Nana Matoba, Jessica T Mory, Justin M Wolter, Michael I Love, Jason L Stein

Abstract read
In one paragraph

Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jordan M Valone *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-0338-4436
Brandon D Le *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nana Matoba *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-5329-0134
Jessica T MoryDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Justin M WolterDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael I LoveDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jason L SteinDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jason_stein@med.unc.edu.ORCID http://orcid.org/0000-0003-4829-0513

Funding

The influence of common genetic variation on brain overgrowth pathwaysR01MH120125 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STEIN, JASON LOUIS · 2019 to 2023
$2.5M
UNC Predoc Training Progr in Bioinformatics/Comp BiologyT32GM067553 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ELSTON, TIMOTHY C · 2005 to 2019
$2.5M
pathQTL: Integrative Multi-Omics Causal Inference of Molecular Mechanisms Leading to Neuropsychiatric IllnessR01MH118349 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LOVE, MICHAEL ISAIAH, STEIN, JASON LOUIS · 2019 to 2023
$2.4M
Quantifying the developmental trajectory of autism-associated brain overgrowth using 3D cellular resolution imagingR01MH121433 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STEIN, JASON LOUIS · 2019 to 2023
$2.2M
Predoctoral Training Program in Bioinformatics and Computational BiologyT32GM135123 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael Isaiah Love, William Valdar · 2021 to 2026
$1.7M
U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM067553U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM135123U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH118349U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH120125U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH121433
6 · The paper itself

Abstract

Gene by treatment (GxT) interactions likely contribute to variability in clinical response, but are difficult to identify in population studies. Here, we applied psychiatric and neurological disorder treatments to a genotyped population of human neural progenitors (n = 83 donors) and measured molecular responses on chromatin accessibility and gene expression. Gene regulatory responses to valproic acid (VPA), which is also a prenatal risk factor for autism, and lithium were highly enriched in genetic risk for psychiatric disorders, demonstrating the convergence of environmental and genetic factors. Genetic variation impacted molecular response to these drugs at over 1000 loci, a subset of which modulated the impacts of psychiatric risk variants. Finally, transcriptome-wide association conducted in the context of VPA revealed genes involved with folate metabolism associated with cognitive ability. As previous work has shown that folate supplementation can alleviate VPA-induced teratogenic effects, this approach identified a validated treatment pathway supporting its broad utility.

Indexed as

LithiumNeural Stem CellsValproic AcidFemaleFolic AcidGene-Environment InteractionGenome-Wide Association StudyHumansMental DisordersPolymorphism, Single NucleotideFolic AcidLithiumValproic Acid

Identifiers

PMID41935183
PMCPMC13364665

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.