Evidence map›Paper›PMID 42814739›Full record

ArticlePLoS genetics2026

Immune markers mediate genetic relationships between immune diseases and psychiatric disorders.

Sophie Breunig, Kristen M Kelly, Lukas S Schaffer, Jeremy M Lawrence, Younga Heather Lee, Elizabeth W Karlson, Andrew D Grotzinger

Abstract read
In one paragraph

Article in PLoS genetics, 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.

Sophie BreunigInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, United States of America.ORCID https://orcid.org/0000-0001-6594-0587
Kristen M KellyInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, United States of America.
Lukas S SchafferInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, United States of America.
Jeremy M LawrenceInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, United States of America.
Younga Heather LeePsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Elizabeth W KarlsonMassachusetts General Hospital Brigham, Boston, Massachusetts, United States of America.
Andrew D GrotzingerInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, United States of America.

Funding

Research Training: Mental Health Behavior GeneticsT32MH016880 · NIMH · UNIVERSITY OF COLORADO AT BOULDER · PI Naomi P. Friedman, Matthew Charles Keller · 1985 to 2026
$5.3M
Longitudinal multi-omic biomarkers for neurocognitive decline prior to dementia onsetU01AG083829 · NIA · UNIVERSITY OF EDINBURGH · PI Sarah Elizabeth Harris · 2024 to 2026
$3.5M
Dissecting the Multivariate Genetic Architecture of Psychiatric DiseasesR01MH120219 · NIMH · UNIVERSITY OF TEXAS AT AUSTIN · PI NIVARD, MICHEL GUILLAUME, TUCKER-DROB, ELLIOT MAX · 2020 to 2024
$3.3M
Large-Scale Genomic Analysis of Aging-Related Cognitive Change Prior to Dementia OnsetR01AG073593 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI TUCKER-DROB, ELLIOT MAX · 2024 to 2025
$1.3M
NIA NIH HHS R01 AG073593NIA NIH HHS U01 AG083829NIMH NIH HHS R01 MH120219NIMH NIH HHS T32 MH016880
6 · The paper itself

Abstract

This study explored the genetic links between 11 immune-mediated diseases and 13 psychiatric disorders, addressing the limited understanding of the underlying biological mechanisms linking these illnesses. Utilizing genomic structural equation modeling, we investigated whether the genetic liability for 14 immune markers (e.g., C-reactive protein [CRP], interleukin-6 [IL-6]) mediated associations between latent genomic factors of immune-mediated diseases (e.g., autoimmune) and psychiatric disorders (e.g., internalizing). While the literature extensively describes the psychiatric relevance of CRP, results indicated this is better explained by its biological precursor, IL-6. This is evidenced by highly attenuated associations of psychiatric traits with CRP when accounting for overlapping signal of IL6. Overall, the genetic liability of six immune markers significantly mediated 11 psychiatric-immune disease genetic relationships. For example, IL-6 mediated 60% of the genetic link between an internalizing factor and Crohn's disease. Identified markers often evinced mediating effects for multiple disorder clusters and many immune-psychiatric relationships were mediated by multiple markers. At the same time, highlighting their diagnostic relevance, only a subset of examined immune markers were significant mediators. These findings provide mechanistic insight by pinpointing the immune markers that may be most critical to the psychiatric-immune disease link, which notably did not include CRP.

Indexed as

Immune System DiseasesMental DisordersBiomarkersC-Reactive ProteinGenetic Predisposition to DiseaseHumansInterleukin-6BiomarkersC-Reactive ProteinInterleukin-6

Identifiers

PMID42814739
PMCPMC13641701

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Registered trials

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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 OpenQuestion graph.