- Title
- No additional prognostic value of genetic information in the prediction of vascular events after cerebral ischemia of arterial origin: The PROMISe study
- Creator
- Achterberg, Sefanja; Kappelle, L. Jaap; Mali, W.P.T.M.; Doevendans, P.A.; Farrall, Martin; Holliday, Elizabeth G.; Sudlow, Cathie; Hopewell, Jemma C.; Cheng, Yu-Ching; Fornage, Myriam; Ikram, M. Arfan; Malik, Rainer; De Bakker, Paul I. W.; Bevan, Steve; Thorsteinsdottir, Unnur; DeStefano, Anita L.; Worrall, Bradford B.; Reiner, Alex P.; Mitchell, Braxtin D.; Clarke, Robert; Levi, Christopher; Seshadri, Sudha; Boncoraglio, Giorgio B.; Traylor, Matthew; Sharma, Pankaj; Bis, Joshua C.; Gretarsdottir, Solveig; Psaty, Bruce M.; Rothwell, Peter M.; Rosand, Jonathan; Meschia, James F.; Stefansson, Kari; Dichgans, Martin; Markus, Hugh S.; Algra, Ale; Van Der Graaf, Y.; Grobbee, D.E.; Rutten, G.E.H.M.; Visseren, F.L.J.; Moll, F.L.
- Relation
- Public Library of Science Vol. 10, Issue 4
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0119203
- Publisher
- Public Library of Science
- Resource Type
- journal article
- Date
- 2015
- Description
- 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. Methods and 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.
- Subject
- genetic information; cerebral ischemia; vascular events; risk factors
- Identifier
- http://hdl.handle.net/1959.13/1340207
- Identifier
- uon:28417
- Identifier
- ISSN:1932-6203
- Rights
- © 2015 Achterberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Language
- eng
- Full Text
- Reviewed
- Hits: 33981
- Visitors: 34428
- Downloads: 576
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 201 KB | Adobe Acrobat PDF | View Details Download |