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December 2018; 4 (6) ArticleOpen Access

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Sara L. Pulit, Lu-Chen Weng, Patrick F. McArdle, Ludovic Trinquart, Seung Hoan Choi, Braxton D. Mitchell, Jonathan Rosand, Paul I. W. de Bakker, Emelia J. Benjamin, Patrick T. Ellinor, Steven J. Kittner, Steven A. Lubitz, Christopher D. Anderson
First published December 3, 2018, DOI: https://doi.org/10.1212/NXG.0000000000000293
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Article Information

vol. 4 no. 6 e293
DOI: 
https://doi.org/10.1212/NXG.0000000000000293
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2376-7839
History: 
  • Received June 23, 2018
  • Accepted in final form September 9, 2018
  • First Published December 3, 2018.
Copyright & Usage: 
Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Sara L. Pulit, PhD,
    2. Lu-Chen Weng, PhD,
    3. Patrick F. McArdle, PhD,
    4. Ludovic Trinquart, PhD,
    5. Seung Hoan Choi, PhD,
    6. Braxton D. Mitchell, PhD,
    7. Jonathan Rosand, MD,
    8. Paul I. W. de Bakker, PhD,
    9. Emelia J. Benjamin, MD, ScM,
    10. Patrick T. Ellinor, MD, PhD,
    11. Steven J. Kittner, MD,
    12. Steven A. Lubitz, MD, MPH* and
    13. Christopher D. Anderson, MD*
    14. on behalf of the Atrial Fibrillation Genetics Consortium and the International Stroke Genetics Consortium
  1. Sara L. Pulit, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Illumina, honoraria for speaking at an Illumina event at the American Society of Human Genetics (2015)

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Illumina, honoraria for speaking at an Illumina event at the American Society of Human Genetics (2015) (same disclosure as above)

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Lu-Chen Weng, PhD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. I receive financial research support from American Heart Association Postdoctoral Fellowship Award 17POST33660226.

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Patrick F. McArdle, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Regeneron

    Research Support, Government Entities:

    1. (1) NINDS, R01NS105150-01, Co-Investigator, 1/15/2018- 12/31/22 (2) NINDS, R01NS100178-01A1, Co-Investigator, 6/1/2017-2/28/22

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Ludovic Trinquart, PhD,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Seung Hoan Choi, PhD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Braxton D. Mitchell, PhD,
    7. Scientific Advisory Boards:

    1. SAB, Non-profit: External Scientific Review Board, Cardiac Health Project (ICHP), Walter Reed National Military Medical Center, Bethesda, MD

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Current Genetic Medicine Reports (Section editor, Cardiovascular Genetics) Frontiers in Neurology (Review Editor, Stroke)

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Regeneron Pharmaceuticals, Inc.

    Research Support, Government Entities:

    1. NIH, NS105150, MPI NIH, NS100178, MPI NIH, HL121007, MPI NIH, P30DK072488, MPI NIH, MH1D8148, CI NIH, NS086905, CI NIH, EB015611, CI NIH, HL137922, CI NIH, HL136574, CI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Jonathan Rosand, MD,
    8. Scientific Advisory Boards:

    1. Pfizer, DSMB

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Lancet Neurology, editorial board member Stroke, editorial board member

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH/NINDS

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. Boehringer Ingelheim, 2017

  8. Paul I. W. de Bakker, PhD,
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Vertex Pharmaceuticals, Senior Director, 2015-present

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Emelia J. Benjamin, MD, ScM,
    10. Scientific Advisory Boards:

    1. Non-profit entity: ?Board: The NIH, NHLBI appointed me to serve on the Outside Safety and Monitoring Board for the NIH, NHLBI?s Coronary Artery Risk Development in Young Adults [CARDIA] Study

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Honorarium From American Heart Association for serving as an Associate Editor for Circulation, 2004-2016. Served until 06/30/2016.

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Non-commercial: a) Boston University School of Medicine, Professor

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. Grants: National Institutes of Health (NIH): R01HL092577; R01HL128914; American Heart Association (AHA)/NIH: P50HL120163; Robert Wood Johnson Foundation: "Mobile Health Technology for Cardiovascular Risk Reduction" AHA: 18SFRN34150007

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Multilevel Mentoring: Boston University School of Medicine Accelerator Plan PI: Emelia J. Benjamin, MD, ScM Period: 11/01/12-10/31/14 Agency: American Council on Education, Alfred P. Sloan Faculty Career Flexibility Award Specific Aims: 1. To create policies and programs that promote career flexibility throughout the life-course of faculty members? careers; 2. Create a midcareer longitudinal faculty development program.

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Patrick T. Ellinor, MD, PhD,
    11. Scientific Advisory Boards:

    1. Bayer AG Novartis Quest Diagnostics

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Bayer AG

    Research Support, Government Entities:

    1. This work was supported by grants from the National Institutes of Health to Dr. Ellinor (1RO1HL092577, R01HL128914, K24HL105780).

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr. Ellinor is also supported by an Established Investigator Award from the American Heart Association (13EIA14220013) and by the Fondation Leducq (14CVD01).

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Steven J. Kittner, MD,
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Editorial Board, Neuroepidemiology, 2000- present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NINDS: R01NS100178, Co-PI, 2017-2022 NINDS: R01NS105150, Co-PI, 2017-2022 NINDS: 2U01NS036695, Site PI, 2016-2021 NINDS: R01NS086905, Site PI, 2015-2020 NINDS: R01NS100417, Site PI, 2017-2022

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Steven A. Lubitz, MD, MPH* and
    13. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Dr. Lubitz has consulted for Abbott, Quest Diagnostics, Bristol Myers Squibb.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Dr. Lubitz has received sponsored research support from Bristol Myers Squibb, Bayer HealthCare, Biotronik, and Boehringer Ingelheim.

    Research Support, Government Entities:

    1. Dr. Lubitz is supported by NIH grant 1R01HL139731.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr. Lubitz is supported by NIH grant 1R01HL139731. Dr. Lubitz is supported by a grant from the American Heart Association 18SFRN34250007, and a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  13. Christopher D. Anderson, MD*
    14. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. ApoPharma, Inc.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) NIH-NINDS K23 NS086873, PI (2) NIH-NINDS R01 NS103924, PI (3) American Heart Association 18SFRN34250007, Co-PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Genetics (S.L.P., P.I.W.d. B.), University Medical Center Utrecht, Utrecht University, The Netherlands; P.I.W.d.B. is now with Computational Genomics, Vertex Pharmaceuticals, Boston, MA; Li Ka Shing Centre for Health Information and Discovery (S.L.P.), The Big Data Institute, University of Oxford, United Kingdom; Program in Medical and Population Genetics (S.L.P., L.-C.W., S.H.C., J.R., P.T.E., S.A.L., C.D.A.), Broad Institute, Cambridge, MA; Cardiovascular Research Center (L.-C.W., P.T.E., S.A.L.), Center for Genomic Medicine (J.R., C.D.A.), J.P. Kistler Stroke Research Center (J.R., C.D.A.), and Cardiac Arrhythmia Service (P.T.E., S.A.L.), Massachusetts General Hospital, Boston; Department of Medicine (P.F.M., B.D.M.), Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (L.T., E.J.B.); Department of Biostatistics (L.T.) and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Geriatrics Research and Education Clinical Center (B.D.M.), Baltimore Veterans Administration Medical Center, MD; Cardiology Preventive Medicine Sections (E.J.B.), Evans Department of Medicine, Boston University School of Medicine; Department of Neurology (S.J.K.), University of Maryland School of Medicine; and Department of Neurology (S.J.K.), Veterans Affairs Medical Center, Baltimore, MD.
  1. Correspondence
    Dr. Lubitz slubitz{at}mgh.harvard.edu or Dr. Anderson cdanderson{at}mgh.harvard.edu
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