ArticleNature cardiovascular research2024
Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease.
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Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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37citing papers in PubMed, 2 pooled it
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37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Shared neuroimaging and molecular profiles in type 2 diabetes mellitus and major depressive disorder: an integrative analysis of genetic, transcriptomic, and neuroimaging data.Translational psychiatry · 2025Pooled it
- Identification ofDepression and anxiety · 2025Pooled it
- Association of long-term depressive burden with incident cardiometabolic multimorbidity: a prospective study in middle-aged and older adults across three continents.Journal of global health · 2026Article
- Big data and psychiatry: advances, constraints and future directions.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- Dissecting pleiotropy between major depressive disorder and physical disease comorbidities.Nature genetics · 2026Article
- Mapping genetic convergence across brain structure, mental health, and cardiometabolic disease.Communications medicine · 2026Article
- Immuno-metabolic depression: challenges ahead for identification and intervention.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- Mental disorders, psychotropic drug dispensation and unfavourable sociodemographic factors in patients with myocardial infarction with and without obstructive coronary arteries.International journal of cardiology. Cardiovascular risk and prevention · 2026Article
- Evidence for overlapping genetic architecture between lifestyle factors and severe mental disorders with different patterns across diagnoses.EBioMedicine · 2026Article
- Genetic perspectives on the comorbidity of anxiety and mood disorders with cardiovascular disease.Nature cardiovascular research · 2026Review
- Familial coaggregation and shared genetic loading of mental disorders and cardiovascular diseases.Psychological medicine · 2026Article
- Transcriptomic insights into the co-occurring psychological symptoms and cardiovascular risks among military service members and veterans with mild traumatic brain injury: A LIMBIC-CENC study.Brain, behavior, & immunity - health · 2026Article
- Brain Aging Mediating Heart Imaging-Derived Phenotypes and Mental and Nervous System Disorders.Aging cell · 2026Article
- Symptom-specific genetics reveal heterogeneity within major depressive disorder.medRxiv : the preprint server for health sciences · 2026Article
- The shared genetic architecture underlying the autoimmune and cardiovascular disease: a multivariate genome-wide analysis.Cardiovascular diabetology · 2026Article
- Heart Rate Variability Biofeedback Alleviates Subthreshold Depression by Reconstructing the Brain-Heart Axis via Habenular Network Functional Connectivity Modulation.CNS neuroscience & therapeutics · 2025Article
- Genome-wide association analyses identify distinct genetic architectures for early-onset and late-onset depression.Nature genetics · 2025Article
- Disease clusters and their genetic determinants following a diagnosis of depression: analyses based on a novel three-dimensional disease network approach.Molecular psychiatry · 2025Article
- A multilayer network analysis of cardiovascular-depression comorbidity reveals symptom-specific molecular biomarkers.Psychological medicine · 2025Article
- Systemic Inflammation at the Crossroad of Major Depressive Disorder and Comorbidities: A Narrative Review.International journal of molecular sciences · 2025Review
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Authors and funding
26 authors.
Jacob Bergstedt *Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. jacob.bergstedt@ki.se.ORCID 0000-0002-9279-6936
Joëlle A Pasman *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ziyan Ma *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7514-7934
Arvid HarderDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Shuyang YaoDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9669-4470
Nadine ParkerCentre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-8369-0152
Jorien L TreurGenetic Epidemiology, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Dirk J A SmitGenetic Epidemiology, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-8301-8860
Oleksandr FreiCentre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-6427-2625
Alexey A ShadrinCentre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
Joeri J MeijsenInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0002-4161-2199
Qing ShenUnit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Per TornvallDepartment of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Alfonso BuilInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0002-3097-1014
Thomas WergeInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0003-1829-0766
Jens Hjerling-LefflerDepartment Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-4539-1776
Thomas D AlsDepartment of Molecular Medicine (MOMA), Molecular Diagnostic Laboratory, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0002-2963-1928
Anders D BørglumDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0001-8627-7219
Cathryn M LewisSocial, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.ORCID 0000-0002-8249-8476
Andrew M McIntoshCentre for Clinical Brain Sciences, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID 0000-0002-0198-4588
Unnur A ValdimarsdóttirUnit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5382-946X
Ole A AndreassenCentre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-4461-3568
Patrick F SullivanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-6619-873X
Yi Lu *Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9933-3654
Fang Fang *Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. fang.fang@ki.se.ORCID 0000-0002-3310-6456
Funding
2/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124851 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI BOERGLUM, ANDERS, DAVIS, LEA K · 2021 to 2025
$5.4MA Trans-Nordic Study of Extreme Major DepressionR01MH123724 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATRICK F SULLIVAN, Lu Yi · 2020 to 2026
$4.7M1/7 PGC: Advancing Discovery and ImpactR01MH124871 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BULIK, CYNTHIA M, SULLIVAN, PATRICK F · 2021 to 2025
$3.5M2/2 Genetics at an extreme: an efficient genomic study of individuals with clinically severe major depression receiving ECTR01MH121545 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2019 to 2023
$2.9MEC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Sklodowska-Curie Actions (H2020 Excellent Science - Marie Sklodowska-Curie Actions) 801133EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 847776EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 964874Lundbeckfonden (Lundbeck Foundation) R155-2014-1724NIMH NIH HHS R01 MH121545NIMH NIH HHS R01 MH123724NIMH NIH HHS R01 MH124851NIMH NIH HHS R01 MH124871U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH121545U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH123724U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH124871U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH123724Vetenskapsrådet (Swedish Research Council) D0886501Wellcome TrustWellcome Trust (Wellcome) 220857/Z/20/Z
Abstract
Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD-atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD-CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD.
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Cardiovascular DiseasesComorbidityGenetic Predisposition to DiseaseGenome-Wide Association StudyMajor Depressive DisorderFemaleHeart Disease Risk FactorsHumansMaleRisk AssessmentRisk Factors
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