Association of impaired renal function with venous thrombosis: A genetic risk score approach

The association between impaired kidney function and venous thrombosis has been previously reported but supportive data are still sparse. We here wish to strengthen this association by investigating, by use of a genetic risk score approach, whether single nucleotide polymorphisms (SNPs) known to decrease the estimated glomerular filtration rate (eGFR), a surrogate marker for renal dysfunction, are associated with increased risk of venous thrombosis.

Fifty-one polymorphisms selected from the literature to robustly associate with eGFR were first tested for association with venous thrombosis in a French case-control collection of 1953 patients and 2338 healthy individuals. This led to the identification of a genetic risk score based on 9 polymorphisms that strongly associated with increased risk (odds ratio (OR)=1.09 [1.06-1.15], p=1.44·10^-7). This genetic score association replicated (OR=1.18 [1.11-1.26], p=8.86·10^-8) in an independent sample of 1289 patients and 1049 healthy controls part of the Dutch MEGA study. We then categorized the genetic score distribution observed in the combined samples into quintiles. Compared with the lowest quintile, the OR for increased risk of disease associated with the second, third, fourth and fifth quintiles were 1.13 [0.94-1.16], 1.47 [1.22-1.77], 1.52 [1.26-1.82] and 1.70 [1.41-2.05], respectively.

Using a genetic risk score analysis, our study provides new elements supporting the association between impaired renal function and the risk of venous thrombosis.