Evidence map›Paper›PMID 34730178›Full record

ArticleSchizophrenia bulletin2022

Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study.

Rada R Veeneman, Jentien M Vermeulen, Abdel Abdellaoui, Eleanor Sanderson, Robyn E Wootton, Rafik Tadros, Connie R Bezzina, Damiaan Denys, Marcus R Munafò, Karin J H Verweij and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Schizophrenia bulletin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% of its field
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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  6. Article
  7. Gut microbiota: contributing to high CVD prevalence in people living with schizophrenia?European archives of psychiatry and clinical neuroscience · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Schizophrenia.Nature reviews. Disease primers · 2025
    Review
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  15. Article
  16. Review
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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

11 authors at 4 institutions in 4 countries.

Rada R VeenemanDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jentien M VermeulenDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Abdel AbdellaouiDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Eleanor SandersonIntegrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID 0000-0001-5188-5775
Robyn E WoottonIntegrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID 0000-0003-3961-3202
Rafik TadrosCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.ORCID 0000-0002-1472-0258
Connie R BezzinaDepartment of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Damiaan DenysDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Marcus R MunafòIntegrative Epidemiology Unit, University of Bristol, Bristol, UK.
Karin J H VerweijDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jorien L TreurDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam University Medical Centers · NLUniversity of Bristol · GBAmsterdam Neuroscience · NLMontreal Heart Institute · CA

Funding

Department of HealthMedical Research Council MC_UU_00011/7
6 · The paper itself

Abstract

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.

Indexed as

Cardiovascular DiseasesCorrelation of DataGenetic TestingHumansMendelian Randomization AnalysisSchizophreniacausalitycoronary artery diseasedilated cardiomyopathyearly repolarizationheart rate variabilityQT interval

Identifiers

PMID34730178
PMCPMC8886584
OpenAlexW3210673974

What OpenQuestion holds

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LicenceCC BY-NC
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 OpenQuestion graph.