Author's Accepted Manuscript
Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation Morten S. Olesen MSc, PhD, Laura Andreasen BM, Javad Jabbari MSc, Lena Refsgaard MD, Stig Haunsø DMSc, MD, Søren-Peter Olesen DMSc, MD, Jonas B. Nielsen MD, Nicole Schmitt MSc,PhD, Jesper H Svendsen DMSc www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(13)01208-3 http://dx.doi.org/10.1016/j.hrthm.2013.10.034 HRTHM5516
To appear in:
Heart Rhythm
Cite this article as: Morten S. Olesen MSc, PhD, Laura Andreasen BM, Javad Jabbari MSc, Lena Refsgaard MD, Stig Haunsø DMSc, MD, Søren-Peter Olesen DMSc, MD, Jonas B. Nielsen MD, Nicole Schmitt MSc,PhD, Jesper H Svendsen DMSc, Very earlyonset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2013.10.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation Short title: Rare variants and atrial fibrillation Morten S. Olesena,b,c MSc, PhD, Laura Andreasena,b,c BM, Javad Jabbaria,b MSc, Lena Refsgaarda,b,c MD, Stig Haunsøa,b,c DMSc, MD, Søren-Peter Olesena,d DMSc, MD, Jonas B. Nielsena,b,c MD, Nicole Schmitta,d MSc, PhD, Jesper H Svendsena,b,c DMSc. a
The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC),
Copenhagen, Denmark b
Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark c
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark d
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark
Address for correspondence: Morten Salling Olesen, MSc, PhD Laboratory for Molecular Cardiology; Rigshospitalet Juliane Mariesvej 9, 2100 Copenhagen Ø, Denmark Phone: +45 35456506, Fax: +45 35456500 Email: [email protected]
FINANCIAL SUPPORT The Danish National Research Foundation, The John and Birthe Meyer Foundation,
Copenhagen, The Research Foundation of the Heart Centre Rigshospitalet, The Arvid Nilsson Foundation, and Director Ib Henriksens Foundation.
CONFLICTS OF INTEREST None. ABSTRACT
Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently, 14 genes important for ion channel function, intercellular signalling, and homeostatic control have been associated with AF. Objective We hypothesized that rare genetic variants in genes previously associated with AF had a higher prevalence in early-onset lone AF patients than in the background population. Methods Sequencing results of KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1,2,5, KCNJ2, SCN1-3B, NPPA, and GJA5 from 192 early-onset lone AF patients were compared with data from the NHLBI Exome Variant Server (EVS) consisting of 6,503 persons from 18 different cohort studies. Results Among the lone AF patients, 29 of the alleles (7.6%) harbored a novel or very rare variant (minor allele frequency [MAF]
Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation Morten S. Olesen MSc, PhD, Laura Andreasen BM, Javad Jabbari MSc, Lena Refsgaard MD, Stig Haunsø DMSc, MD, Søren-Peter Olesen DMSc, MD, Jonas B. Nielsen MD, Nicole Schmitt MSc,PhD, Jesper H Svendsen DMSc www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(13)01208-3 http://dx.doi.org/10.1016/j.hrthm.2013.10.034 HRTHM5516
To appear in:
Heart Rhythm
Cite this article as: Morten S. Olesen MSc, PhD, Laura Andreasen BM, Javad Jabbari MSc, Lena Refsgaard MD, Stig Haunsø DMSc, MD, Søren-Peter Olesen DMSc, MD, Jonas B. Nielsen MD, Nicole Schmitt MSc,PhD, Jesper H Svendsen DMSc, Very earlyonset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2013.10.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation Short title: Rare variants and atrial fibrillation Morten S. Olesena,b,c MSc, PhD, Laura Andreasena,b,c BM, Javad Jabbaria,b MSc, Lena Refsgaarda,b,c MD, Stig Haunsøa,b,c DMSc, MD, Søren-Peter Olesena,d DMSc, MD, Jonas B. Nielsena,b,c MD, Nicole Schmitta,d MSc, PhD, Jesper H Svendsena,b,c DMSc. a
The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC),
Copenhagen, Denmark b
Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark c
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark d
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark
Address for correspondence: Morten Salling Olesen, MSc, PhD Laboratory for Molecular Cardiology; Rigshospitalet Juliane Mariesvej 9, 2100 Copenhagen Ø, Denmark Phone: +45 35456506, Fax: +45 35456500 Email: [email protected]
FINANCIAL SUPPORT The Danish National Research Foundation, The John and Birthe Meyer Foundation,
Copenhagen, The Research Foundation of the Heart Centre Rigshospitalet, The Arvid Nilsson Foundation, and Director Ib Henriksens Foundation.
CONFLICTS OF INTEREST None. ABSTRACT
Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently, 14 genes important for ion channel function, intercellular signalling, and homeostatic control have been associated with AF. Objective We hypothesized that rare genetic variants in genes previously associated with AF had a higher prevalence in early-onset lone AF patients than in the background population. Methods Sequencing results of KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1,2,5, KCNJ2, SCN1-3B, NPPA, and GJA5 from 192 early-onset lone AF patients were compared with data from the NHLBI Exome Variant Server (EVS) consisting of 6,503 persons from 18 different cohort studies. Results Among the lone AF patients, 29 of the alleles (7.6%) harbored a novel or very rare variant (minor allele frequency [MAF]
