Pulmonary vascular disease & thromboembolismMeta-analysis
Genetically Mediated Differences in Low-density Lipoprotein (LDL) Cholesterol and Risk of Venous Thromboembolism
- Genetic association study (whole-genome sequencing, Mendelian randomization)
- 2 biobanks
- fixed-effect meta-analysis
- rare variant burden
- multivariable Mendelian randomization
Authors' conclusion
Across 2 large biobanks, genetically mediated differences in LDL-C were not consistently associated with VTE risk, suggesting that genetically mediated differences in LDL-C are unlikely to exert a large effect on venous thrombosis risk, although small effects cannot be excluded.
Study context
- Population
- UK Biobank and All of Us participants with whole-genome sequencing430,049 UK Biobank + 283,609 All of Us
- Comparison
- Carriers of rare functional LDLR, APOB, PCSK9 variants vs non-carriers
- Outcome
- VTE
Pooled result
As reported in the abstract
Rare variants produced gene-specific low-density lipoprotein cholesterol (LDL-C) differences
up to ∼50% differences
Meta-analyzed ORs ranged
0.60 to 1.07
Further pooled results
Sensitivity and prospective (incident venous thromboembolism (VTE)) analyses
- Similar findings
Common variant and multivariable Mendelian randomization analyses
- Previously reported LDL-C associations with VTE may partly reflect broader metabolic and obesity-related pathways
Positive control: established thrombophilia variants
- Expected associations demonstrated
Original publication
Summarised from the published abstract; every number is checked against it