- Title
- Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies
- Creator
- Malik, Rainer; Bevan, Steve; de Stefano, Anita L.; Fornage, Myriam; Psaty, Bruce M.; Ikram, M. Afran; Launer, Lenore J.; Van Duijn, Cornelia M.; Sharma, Pankaj; Mitchell, Braxton D.; Rosand, Jonathan; Meschia, James F.; Nalls, Michael A.; Levi, Christopher; Rothwell, Peter M.; Sudlow, Cathie; Markus, Hugh S.; Seshadri, Sudha; Dichgans, Martin; MD Wellcome Trust Case Control Consortium 2,; Holliday, Elizabeth G.; Devan, William J.; Cheng, Yu-Ching; Ibrahim-Verbaas, Carla A.; Verhaaren, Benjamin F. J.; Bis, Joshua C.; Joon, Aron Y.
- Relation
- Stroke Vol. 45, Issue 2, p. 394-402
- Publisher Link
- http://dx.doi.org/10.1161/STROKEAHA.113.002938
- Publisher
- Lippincott Williams & Wilkins
- Resource Type
- journal article
- Date
- 2014
- Description
- Background and Purpose - Genome-wide association studies have revealed multiple common variants associated with known risk factors for ischemic stroke (IS). However, their aggregate effect on risk is uncertain. We aimed to generate a multilocus genetic risk score (GRS) for IS based on genome-wide association studies data from clinical-based samples and to establish its external validity in prospective population-based cohorts. Methods - Three thousand five hundred forty-eight clinic-based IS cases and 6399 controls from the Wellcome Trust Case Control Consortium 2 were used for derivation of the GRS. Subjects from the METASTROKE consortium served as a replication sample. The validation sample consisted of 22 751 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. We selected variants that had reached genome-wide significance in previous association studies on established risk factors for IS. Results - A combined GRS for atrial fibrillation, coronary artery disease, hypertension, and systolic blood pressure significantly associated with IS both in the case-control samples and in the prospective population-based studies. Subjects in the top quintile of the combined GRS had >2-fold increased risk of IS compared with subjects in the lowest quintile. Addition of the combined GRS to a simple model based on sex significantly improved the prediction of IS in the combined clinic-based samples but not in the population-based studies, and there was no significant improvement in net reclassification. Conclusions - A multilocus GRS based on common variants for established cardiovascular risk factors was significantly associated with IS both in clinic-based samples and in the general population. However, the improvement in clinical risk prediction was found to be small.
- Subject
- genetics; genetic polymorphism; risk assessment; resk factors
- Identifier
- http://hdl.handle.net/1959.13/1295515
- Identifier
- uon:19050
- Identifier
- ISSN:0039-2499
- Language
- eng
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