Multilocus Genetic Risk Score Associates With Ischemic Stroke in Case-Control and Prospective Cohort Studies

作者：Malik Rainer; Bevan Steve; Nalls Michael A; Holliday Elizabeth G; Devan William J; Cheng Yu Ching; Ibrahim Verbaas Carla A; Verhaaren Benjamin F J; Bis Joshua C; Joon Aron Y; de Stefano Anita L; Fornage Myriam; Psaty Bruce M; Ikram M Arfan; Launer Lenore J; van Duijn Cornelia M; Sharma Pankaj; Mitchell Braxton D; Rosand Jonathan; Meschia James F; Levi Christopher; Rothwell Peter M; Sudlow Cathie; Markus Hugh S; Seshadri Sudha; Dichgans Martin^*

来源：Stroke, 2014, 45(2): 394-402.

DOI：10.1161/STROKEAHA.113.002938

• genetics
• polymorphism
• genetic
• risk assessment
• risk factors

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. %26lt;br%26gt;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. %26lt;br%26gt;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 %26gt;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. %26lt;br%26gt;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.

• 出版日期2014-2
• 单位上海生物信息技术研究中心