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Published in: Journal of Thrombosis and Thrombolysis 1/2022

Open Access 01-01-2022

Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

Authors: Shuai Yuan, Maria Bruzelius, Susanna C. Larsson

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2022

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Abstract

Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.
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Metadata
Title
Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation
Authors
Shuai Yuan
Maria Bruzelius
Susanna C. Larsson
Publication date
01-01-2022
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 1/2022
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-021-02494-4

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