Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

Stroke
Authors
Keywords
Abstract

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors.

METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke.

RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P

CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Year of Publication
2014
Journal
Stroke
Volume
45
Issue
2
Pages
403-12
Date Published
2014 Feb
ISSN
1524-4628
URL
DOI
10.1161/STROKEAHA.113.003044
PubMed ID
24436238
PubMed Central ID
PMC3955258
Links
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R01 DK078616 / DK / NIDDK NIH HHS / United States
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N01HC55222 / HC / NHLBI NIH HHS / United States
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N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
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