Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke.

Stroke
Authors
Keywords
Abstract

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF.

METHODS: In 27 471 participants of the Malmö Diet and Cancer Study, a prospective, community-based cohort, we used Cox models that adjusted for established AF risk factors to assess the association of AF-GRS with incident AF and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5 years for ischemic stroke. The AF-GRS comprised 12 single nucleotide polymorphisms that had been previously shown to be associated with AF at genome-wide significance.

RESULTS: During follow-up, 2160 participants experienced a first AF event and 1495 had a first ischemic stroke event. Participants in the top AF-GRS quintile were at increased risk for incident AF (hazard ratio, 2.00; 95% confidence interval, 1.73-2.31; P=2.7×10(-21)) and ischemic stroke (hazard ratio, 1.23; 95% confidence interval, 1.04-1.46; P=0.02) when compared with the bottom quintile. Addition of the AF-GRS to established AF risk factors modestly improved both discrimination and reclassification (P

CONCLUSIONS: An AF-GRS can identify 20% of individuals who are at ≈2-fold increased risk for incident AF and at 23% increased risk for ischemic stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful.

Year of Publication
2014
Journal
Stroke
Volume
45
Issue
10
Pages
2856-62
Date Published
2014 Oct
ISSN
1524-4628
URL
DOI
10.1161/STROKEAHA.114.006072
PubMed ID
25123217
PubMed Central ID
PMC4346099
Links
Grant list
282255 / European Research Council / International
K23 HL114724 / HL / NHLBI NIH HHS / United States
1K23HL114724 / HL / NHLBI NIH HHS / United States