Evidence map›Paper›PMID 42202747›Full record

ArticleEBioMedicine2026

Evidence for overlapping genetic architecture between lifestyle factors and severe mental disorders with different patterns across diagnoses.

Linn Rødevand, Zillur Rahman, Piotr Jaholkowski, Nadine Parker, Unnur Anna Valdimarsdóttir, Olav Bjerkehagen Smeland, Markos Tesfaye, Pravesh Parekh, Oleksandr Frei, Srdjan Djurovic and 4 more

Abstract read
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In one paragraph

Article in EBioMedicine, 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

14 authors.

Linn RødevandCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: l.n.rodevand@medisin.uio.no.
Zillur RahmanCentre 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.
Nadine ParkerCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Unnur Anna ValdimarsdóttirInstitute of Environmental Medicine, Unit of Integrative Epidemiology, Karolinska Institute, Stockholm, Sweden; Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Olav Bjerkehagen SmelandCentre 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; Institute for Genomics in Health & Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Pravesh ParekhCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Multimodal Imaging and Genetics, J. Craig Venter Institute, La Jolla, CA, USA.
Oleksandr FreiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway.
Srdjan DjurovicCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Nils Eiel SteenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Clinical Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Division of Mental Health and Substance abuse, Diakonhjemmet Hospital, Oslo, Norway.
Anders Martin DaleCenter for Multimodal Imaging and Genetics, J. Craig Venter Institute, La Jolla, CA, USA; Oslo University Hospital, Oslo, Norway; University of California San Diego, La Jolla, CA, USA.
Alexey ShadrinCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ole Andreas AndreassenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: ole.andreassen@medisin.uio.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSevere mental disorders (SMDs) are associated with unhealthy lifestyle, contributing to increased risk of comorbid cardiovascular disease. Genetic factors influence both SMDs and lifestyle behaviours, but their genetic relationships remain unclear. Here, we aimed to unravel the shared genetic architecture of SMDs and lifestyle factors. Additionally, we assessed if genetic propensity to SMDs predicts body mass index (BMI) and lipids through lifestyle factors.

methodsWe analysed genome-wide data on major depression (MD) (N = 480,359), schizophrenia (SCZ) (N = 130,644), bipolar disorder (BIP) (N = 353,889) and self-reported lifestyle factors (N = 266,048-606,820), including food intake, physical activity, sedentary behaviours, and accelerometer-assessed activity from All of Us (N = 30,132) and UK Biobank (N = 91,105) to obtain objective measures for sensitivity analysis. We estimated the shared genetic architecture using bivariate MiXeR. Shared genetic loci were identified using conjunctional false discovery rate and mapped to genes, which were subject to enrichment analyses. We applied structural equation modelling (SEM) to assess if lifestyle mediates the relationship between polygenic risk score for SMDs and BMI and lipids. People with lived experience were involved in the research.

findingsThere was extensive genetic overlap between lifestyle factors and SMDs, with different patterns of effects. MD was genetically correlated with less physical activity and more sedentary behaviour. SCZ and BIP displayed opposite patterns with genetic associations with less sedentary behaviour, more physical activity and healthier food intake. This divergent pattern across SMDs was largely consistent using accelerometer-assessed activity. We identified 551 shared loci, implicating biological processes related to neurodevelopment and synaptic and neuronal properties. Further analyses indicated that lifestyle factors partly mediate the relationship between genetic risk for SMDs and BMI and lipids.

interpretationThe results show a genetic propensity towards unhealthier lifestyle behaviours in MD, while SCZ and BIP displayed a divergent pattern. The genetic correlations reflecting mixed effect directions may also imply subgroups with different genetic propensity, which can form the basis for risk stratification and more tailored lifestyle interventions and personalised treatment.

fundingResearch Council of Norway (grants, 273291, 273446, 300309, 324252, and 326813), South-East Norway Regional Health Authority (grants 2023-031 and 2022-073), NordForsk (University Cooperation Grant 164218, PreciMENT), European Union's Horizon 2020 Research and Innovation Programme (grant 847776, CoMorMent; grant 964874, RealMent), and the National Institutes of Health (grant R01MH125938).

Indexed as

Life StyleMental DisordersBipolar DisorderBody Mass IndexFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyHumansMajor Depressive DisorderMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsSchizophreniaBipolar disorderBody mass indexGWASLifestyleMajor depressionSchizophrenia

Identifiers

PMID42202747
PMCPMC13233568

What Socratic holds

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LicenceCC BY
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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 Socratic graph.