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Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms

Steven A Lubitz1, Owen E Parsons2, Christopher D Anderson2

  • 1From the Stroke Research Center (C.D.A., J.R.), Center for Human Genetic Research (C.D.A., J.R.), and Cardiovascular Research Center (S.A.L., L.-C.W., P.T.E.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, The Broad Insitute of Harvard and MIT, Cambridge, MA (S.A.L., L.-C.W., C.D.A., J.R., P.T.E.); Autism Research Centre (O.E.P.) and Department of Clinical Neurosciences (H.S.M., M.T.), University of Cambridge, United Kingdom; Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, MA (E.J.B.); Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, MA (E.J.B.); Department of Epidemiology, Boston University School of Public Health, MA (E.J.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians Universität, Germany (R.M., M.D.); Munich Cluster of Systems Neurology (SyNergy), Germany (M.D.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom (C.L.S.); and Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, United Kingdom (P.M.R.). slubitz@mgh.harvard.edu.

Stroke
|May 5, 2017
PubMed

Insights

Genetic predisposition to atrial fibrillation (AF) is strongly linked to cardioembolic stroke but not other stroke types. This finding may improve stroke subtype classification and risk assessment.

Area of Science:

  • Genetics
  • Neurology
  • Cardiology

Background:

  • Atrial fibrillation (AF) is a primary cause of cardioembolic stroke.
  • The link between AF and non-cardioembolic stroke subtypes remains unclear.
  • AF has a significant genetic component, suggesting a potential genetic predisposition.

Purpose of the Study:

  • To investigate the association between genetic predisposition to AF and different ischemic stroke subtypes.
  • To determine if genetic risk for AF can help differentiate stroke causes.

Main Methods:

  • Utilized logistic regression to analyze data from 2374 ischemic stroke patients and 5175 controls.
  • Calculated AF genetic risk scores using single-nucleotide polymorphisms (SNPs) associated with AF.
  • Examined associations across cardioembolic, large vessel, small vessel, and undetermined stroke subtypes.

Main Results:

  • AF genetic risk scores showed a significant association with stroke overall.
  • The strongest association between AF genetic risk and stroke was observed in the cardioembolic stroke subset.
  • No significant association was found between AF genetic risk and non-cardioembolic stroke subtypes.

Conclusions:

  • Genetic risk scores for AF are specific to cardioembolic stroke.
  • Potential misclassification and incomplete workups may affect findings for undetermined stroke.
  • Further research is needed to evaluate AF genetic risk as a biomarker for stroke pathogenesis discrimination.
Abstract

Keywords:
atrial fibrillationgeneticsrisk factorssingle-nucleotide polymorphismstroke

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