Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism.
Blood Adv
; 7(18): 5341-5350, 2023 09 26.
Article
em En
| MEDLINE
| ID: mdl-37399490
ABSTRACT
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Transtorno Bipolar
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Transtorno Depressivo Maior
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Tromboembolia Venosa
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article