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Clinical and Genetic Determinants of Varicose Veins
Study Questions:
What are the clinical and genetic risk factors associated with varicose vein development?
Methods:
The authors applied machine learning to search for risk factors of varicose veins in the UK Biobank population of 493,519 individuals. Predictors were then studied using univariable and multivariable Cox regression. A genome-wide association study was also performed in 337,536 unrelated individuals of white British descent, including assessing for a causal role of height.
Results:
The machine learning approach confirmed age, sex, obesity, pregnancy, and a history of deep vein thrombosis as predictors of varicose veins. It also identified height as a potential risk factor, which was confirmed in traditional multivariable Cox regression (hazard ratio 1.74 for upper vs. lower quartile, 95% confidence interval 1.51-2.01). The genome-wide association study identified 30 new significant loci, including pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis supported the finding that increased height is associated with varicose vein development (odds ratio 1.25, p = 2.07 x 10-16).
Conclusions:
The authors identified novel clinical and genetic risk factors for varicose vein development, including increasing height.
Perspective:
The authors used a comprehensive and complementary approach to identify both clinical and genetic risk factors for varicose vein development. Importantly, they were able to identify and confirm height as an important risk factor in both traditional clinical and genetic-based analyses. While unlikely to immediately impact clinical care, this study provides insight into new causal mechanisms and potential preventative options for varicose vein development.
Keywords: Body Height, Genetics, Genome-Wide Association Study, Obesity, Pregnancy, Primary Prevention, Risk Factors, Varicose Veins, Vascular Diseases, Venous Thrombosis
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