Background: Coagulation allelic variants associated with venous thromboembolism (VTE) have been suggested to be involved in the pathogenesis of ischemic stroke. This nationwide study aimed at determining whether VTE shares familial susceptibility with ischemic stroke.
Method and results: The Swedish Multigeneration Register of 0- to 75-year-old subjects was linked to the Swedish Hospital Discharge Register and the Cause of Death Register for the period 1987 to 2007. Odds ratios (ORs) for VTE and ischemic stroke were determined in 2 ways: odds of ischemic stroke in offspring whose parents had been diagnosed with VTE, and odds of VTE in offspring whose parents had been diagnosed with ischemic stroke. The analyses were repeated for siblings and spouses. Offspring of parents with VTE (n=25,929) were at increased risk for ischemic stroke (n=5595): OR, 1.10 (95% confidence interval [CI], 1.06-1.14). Siblings of probands with VTE (n=45,132) had no increased risk of ischemic stroke (n=1716): OR, 1.05 (95% CI, 1.00-1.11). Spouses of probands with VTE (n=24,106) were at increased risk for ischemic stroke (n=940): OR, 1.18 (95% CI, 1.10-1.27). The risks for VTE in relatives of probands with ischemic stroke were OR, 1.15; 95% CI, 1.10-1.21 (offspring); OR, 1.07; 95% CI, 1.02-1.12 (siblings); and OR, 1.21; 95% CI, 1.11-1.32 (spouses).
Conclusions: VTE does not share strong familial susceptibility with ischemic stroke in the Swedish population. Moreover, familial nongenetic factors contribute to the observed weak familial associations. The present study suggests that it is unlikely that strong shared disease-causing mutations exist to a large extent in the Swedish population.