title: No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study.
abstract: BACKGROUND
  Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information.
  
  
  RESULTS
  We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.
  
  
  CONCLUSIONS
  We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.
authors.affiliation: Department of Neurology and Neurosurgery, Utrecht Stroke Center, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sefanja
authors.initials: S
authors.lastname: Achterberg
authors.affiliation: Department of Neurology and Neurosurgery, Utrecht Stroke Center, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
authors.affiliation: Department of Neurology and Neurosurgery, Utrecht Stroke Center, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001158:Arteries / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics*; D002544:Cerebral Infarction / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D020521:Stroke / Q000235:genetics; D014652:Vascular Diseases / Q000235:genetics*