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Association of polygenic risk scores for severe mental illness with risk of venous thromboembolism

1University of Glasgow, Glasgow, Scotland, United Kingdom, 2University of Edinburgh, Edinburgh, Scotland, United Kingdom, 3Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Barcelona, Catalonia, Spain

Abstract Number: OC 42.5

Meeting: ISTH 2022 Congress

Theme: Venous Thromboembolism » Genetic Risk Factors of Thrombosis

Background: Individuals with severe mental illness (SMI, including schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD)) have an increased risk of metabolic and cardiovascular diseases, including venous thromboembolism (VTE). There is growing evidence from genetic studies that SMI and cardiometabolic diseases share some pathological mechanisms.

Aims: The aim of this study was to determine whether genetic risk for SMI was associated with risk of VTE.

Methods: Using the large population-based UK Biobank, we calculated genome-wide polygenic risk scores (PRS) for MDD, BD and SCZ based on the largest meta-analyses results from the Psychiatric Genomics consortium. These were assessed for impact on VTE risk (self-reported deep vein thrombosis and/or pulmonary embolism, case N&#3f10786, control N&#3f285124), adjusting for age, sex, eight genetic principal components and genotyping chip. Secondary analyses included further adjustment for BMI, smoking, blood group, hormonal therapy and anti-psychotic medication, exclusion of individuals with self-reported SMI and sex-stratified analyses.

Results: In self-reported unrelated white British ancestry participants, PRS of MDD or BD-increasing genetic variants were associated with increased risk of VTE (OR per SD of PRS=1.08 (CIs 1.06-1.10), p < 0.001 and 1.03 (1.01-1.06) p=0.002, respectively). The association was independent of age, sex, population structure, blood group, BMI, smoking, anti-psychotic medication and exogenous hormones (women only). No association was observed between a PRS of SCZ-increasing genetic variants and risk of VTE. Substituting family history of MDD for the PRS showed similar results.

Conclusion(s): Genetic loading for MDD and BD, but not SCZ was associated with an increased risk of VTE. If replicated, these results suggest that family history of SMI (in the absence of genetic data) should be considered in risk assessments of VTE.

To cite this abstract in AMA style:

Strawbridge R, Ward J, Cullen B, Graham N, Anderson J, Pell J, Lyall D, Lyall L, Smith D, Sabater-Lleal M. Association of polygenic risk scores for severe mental illness with risk of venous thromboembolism [abstract]. https://abstracts.isth.org/abstract/association-of-polygenic-risk-scores-for-severe-mental-illness-with-risk-of-venous-thromboembolism/. Accessed October 1, 2023.

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