Evidence map›Paper›PMID 41650220›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Identifying genome-by-childhood trauma interactions for depression using a forest-based approach in the UK Biobank and Adolescent Brain Cognitive Development Study.

Yue Hu, Jeffrey R Gruen, Heping Zhang

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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

3 authors.

Yue HuDepartment of Biostatistics, Yale University School of Public Health, New Haven, CT 06520.ORCID 0009-0002-2126-7559
Jeffrey R GruenDepartment of Pediatrics and of Genetics, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0001-7640-2071
Heping ZhangDepartment of Biostatistics, Yale University School of Public Health, New Haven, CT 06520.ORCID 0000-0002-0688-4076

Funding

VALIDITY OF SUBTYPES OF ADHDP50HD027802 · NICHD · UNIVERSITY OF COLORADO AT BOULDER · PI ERIK G WILLCUTT · 1990 to 2026
$44.9M
THE FLORIDA LONGITUDINAL STUDYP50HD052120 · NICHD · FLORIDA STATE UNIVERSITY · PI TIFFANY P HOGAN, Nicole Sandi Patton-Terry · 2006 to 2026
$31.7M
GENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2M
Analysis of Genomic and Complex DataR01HG010171 · NHGRI · YALE UNIVERSITY · PI ZHANG, HEPING · 2019 to 2022
$1.4M
HHS | NIH | National Human Genome Research Institute (NHGRI) R01HG010171HHS | NIH | National Institute on Aging (NIA) P30AG021342-22S1NHGRI NIH HHS R01 HG010171NICHD NIH HHS P50 HD027802NICHD NIH HHS P50 HD052120NICHD NIH HHS T32 HD007149NSF | Directorate for Mathematical and Physical Sciences (MPS) DMS-2112711
6 · The paper itself

Abstract

Depression is shaped by both genetic and environmental factors, but genome-wide interaction studies (GWIS) often lack power to detect complex gene-environment (G × E) interactions. We applied a forest-based machine learning approach to 38,018 UK Biobank (UKB) participants, examining interactions between 285,677 single-nucleotide polymorphisms (SNPs) and three trauma types (childhood, adult, and catastrophic trauma). While GWIS detected no significant interactions, we identified 8,225 potentially important SNP-environment pairs across 1,732 genes, with childhood trauma contributing most prominently. Stratified heritability was higher among childhood trauma-exposed individuals (13.3%) versus those unexposed (6.0%). Many identified genes overlapped with known psychiatric risk loci and accounted for most of the SNP-based heritability. Thirteen top genes were replicated in the Adolescent Brain Cognitive Development Study. Our findings highlight the polygenic G × E nature of depression and the critical role of childhood trauma in modulating genetic risk, demonstrating the value of forest-based methods in detecting complex gene-environment interactions.

Indexed as

BrainDepressionGene-Environment InteractionAdolescentCognitionFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideUK BiobankUnited Kingdomchildhood traumadepressiongene–environment interactionrandom forest

Identifiers

PMID41650220
PMCPMC12890833

What Socratic holds

Textmetadata
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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.