GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke

Stroke. 2017 May;48(5):1147-1153. doi: 10.1161/STROKEAHA.116.014322. Epub 2017 Apr 14.


Background and purpose: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS.

Methods: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method.

Results: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03).

Conclusions: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

Keywords: genetics; ischemic attack, transient; recurrence; risk factors; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Ischemia / diagnosis
  • Brain Ischemia / genetics*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / genetics*
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / genetics
  • Male
  • North America
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Recurrence
  • Risk
  • Scotland
  • Spain
  • Stroke / diagnosis
  • Stroke / genetics*