Evidence mapPaperPMID 41023670Full record

ArticleGenome medicine2025

Distinct patterns of genetic overlap among multimorbidities revealed with trivariate MiXeR.

Alexey A Shadrin, Guy Hindley, Espen Hagen, Nadine Parker, Markos Tesfaye, Piotr Jaholkowski, Zillur Rahman, Gleda Kutrolli, Vera Fominykh, Srdjan Djurovic and 6 more

Abstract read
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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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

16 authors.

Alexey A ShadrinCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. a.a.shadrin@medisin.uio.no.
Guy HindleyCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Espen HagenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Nadine ParkerCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Markos TesfayeCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Piotr JaholkowskiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Zillur RahmanCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Gleda KutrolliCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Vera FominykhCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Srdjan DjurovicDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Olav B SmelandCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Kevin S O'ConnellCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Dennis van der MeerCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Oleksandr FreiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ole A Andreassen *Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no.
Anders M Dale *Department of Radiology, University of California, San Diego, La Jolla, CA, 92093, USA. andersmdale@gmail.com.

Funding

3/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124839 · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2025 to 2025
$301k
European Union's Horizon 2020 Research and Innovation Programme 801133European Union's Horizon 2020 Research and Innovation Programme 964874Helse Sør-Øst RHF 2022073KG Jebsen Stiftelsen, The South-East Norway Regional Health Authority 2022-087NIH HHS 5R01MH124839-02NIH HHS R01MH123724-01NIMH NIH HHS R01 MH123724NIMH NIH HHS R01 MH124839Norges Forskningsråd 326813Norges Forskningsråd 334920The European Economic Area and Norway Grants EEA-RO-NO-2018-0573
6 · The paper itself

Abstract

backgroundMultimorbidities are a global health challenge. Accumulating evidence indicates that overlapping genetic architectures underlie comorbid complex human traits and disorders. This can be quantified for a pair of phenotypes using various techniques. Still, the pattern of genetic overlap between three distinct complex phenotypes, which is important for understanding multimorbidities, has not been possible to quantify.

methodsHere, we present and validate the novel trivariate MiXeR tool, which disentangles the pattern of genetic overlap between three complex phenotypes using summary statistics from genome-wide association studies. Our simulations show that trivariate MiXeR can reliably reconstruct different patterns of genetic overlap and estimate the proportions of genetic overlap between three phenotypes.

resultsWe found substantial genetic overlap between gastro-intestinal and brain diseases supporting a genetic basis of the gut-brain axis-the pattern consistent with pairwise analysis. However, the pattern of genetic overlap between three diverse cardiometabolic and renal health indicators and three immune-linked disorders revealed a much larger genomic component shared between all phenotypes than expected from separate pairwise analyses. This suggests the existence of core pathways underlying distinct but related chronic conditions.

conclusionsOverall, trivariate MiXeR offers a novel and efficient tool for investigating patterns of genetic overlap among three complex phenotypes. This contributes to a better understanding of genetic relationships between complex traits and disorders, potentially providing new insights into the mechanisms underlying common multimorbidities. Trivariate MiXeR is freely available at https://github.com/precimed/mix3r .

Indexed as

Genetic Predisposition to DiseaseMultimorbiditySoftwareGenome-Wide Association StudyHumansPhenotypeComplex phenotypesGWASMultimorbidityThe pattern of genetic overlapTrivariate MiXeR

Identifiers

PMID41023670
PMCPMC12482798

What Socratic holds

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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 Socratic graph.