Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23

View ORCID ProfileSophie Garnier, Magdalena Harakalova, Stefan Weiss, Michal Mokry, Vera Regitz-Zagrosek, Christian Hengstenberg, Thomas P Cappola, Richard Isnard, Eloisa Arbustini, Stuart A. Cook, Jessica van Setten, Jörg Callis, Hakon Hakonarson, Michael P Morley, Klaus Stark, Sanjay K. Prasad, Jin Li, Declan P O’Regan, Maurizia Grasso, Martina Müller-Nurasyid, Thomas Meitinger, Jean-Philippe Empana, Konstantin Strauch, Mélanie Waldenberger, Kenneth B Marguiles, Christine E. Seidman, Benjamin Meder, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Jeanette Erdman, Stefan Blankenberg, Thomas Wichter, Volker Ruppert, Luigi Tavazzi, Olivier Dubourg, Gerard Roizes, Richard Dorent, Pascal DeGroote, Laurent Fauchier, Jean-Noël Trochu, Jean-François Aupetit, Marine Germain, Uwe Völker, Hemerich Daiane, Ibticem Raji, Delphine Bacq-Daian, Carole Proust, Kristin Lehnert, Renee Maas, Robert Olaso, Ganapathivarma Saripella, Stephan B. Felix, Steven Mc Ginn, Laëtitia Duboscq-Bidot, Alain van Mil, Céline Besse, Vincent Fontaine, Hélène Blanché, Brendan Keating, Pablo Garcia-Pavia, Angélique Curjol, Anne Boland, Michel Komajda, François Cambien, Jean-François Deleuze, Marcus Dörr, Folkert W Asselbergs, Eric Villard, David-Alexandre Trégouët, View ORCID ProfilePhilippe Charron, On behalf of GENMED consortium
doi: https://doi.org/10.1101/2020.02.28.969147
Sophie Garnier
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sophie Garnier
  • For correspondence: sophie.garnier@sorbonne-universite.fr philippe.charron@aphp.fr
Magdalena Harakalova
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
4Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan Weiss
5Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany
6DZHK (German Centre for Cardiovascular Research), partnersite Greifswald, Greifswald, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michal Mokry
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
7Laboratory of Clinical Chemistry and Haematology, University Medical Center, Heidelberglaan 100, Utrecht, The Netherlands
8Laboratory of Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vera Regitz-Zagrosek
9Institute of Gender in Medicine and Center for Cardiovascular Research, Charite University Hospital, Berlin, Germany
10DZHK (German Center for Cardiovascular Research), Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Hengstenberg
11Department of Internal Medicine, Division of Cardiology, Medical University of Vienna, Austria
12Department of Internal Medicine, Medical University of Regensburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas P Cappola
13Penn Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Isnard
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
14APHP, Pitié-Salpêtrière Hospital, Cardiology Department, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eloisa Arbustini
15IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stuart A. Cook
16National Heart and Lung Institute, Imperial College London, London, UK
17National Heart Centre Singapore, Singapore
18Duke-NUS, Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica van Setten
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jörg Callis
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
4Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hakon Hakonarson
19Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael P Morley
13Penn Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Klaus Stark
20Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sanjay K. Prasad
17National Heart Centre Singapore, Singapore
21Royal Brompton Hospital, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jin Li
19Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Declan P O’Regan
22Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maurizia Grasso
23Centre for Inherited Cardiovascular Diseases - IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martina Müller-Nurasyid
24Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
25Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany
26Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Meitinger
24Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
25Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany
27Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Philippe Empana
28Université de Paris, INSERM, UMR-S970, Integrative Epidemiology of cardiovascular disease, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Konstantin Strauch
24Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
25Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany
29Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55101 Mainz, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mélanie Waldenberger
30Research unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
31DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth B Marguiles
13Penn Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine E. Seidman
32Department of Medecine and Genetics Harvard Medical School, Boston, USA
33Brigham & Women’s Cardiovascular Genetics Center, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin Meder
34Institute for Cardiomyopathies Heidelberg, Heidelberg University, Germany & Stanford Genome Technology Center, Department of Genetics, Stanford Medical School, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pierre Boutouyrie
28Université de Paris, INSERM, UMR-S970, Integrative Epidemiology of cardiovascular disease, Paris, France
35APHP, Georges Pompidou European Hospital, Cardiology Department, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Lacolley
36INSERM U1116, Faculté de Médecine, Vandoeuvre-les-Nancy, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xavier Jouven
28Université de Paris, INSERM, UMR-S970, Integrative Epidemiology of cardiovascular disease, Paris, France
35APHP, Georges Pompidou European Hospital, Cardiology Department, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeanette Erdman
37Medizinische Klinik und Poliklinik, Universitätsmedizin der Johannes-Gutenberg Universität Mainz, Mainz, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan Blankenberg
38Medizinische Klinik II, Universität Lübeck, Lübeck, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Wichter
39Dept. of Cardiology and Angiology Niels-Stensen-Kliniken Marienhospital Osnabrück, Heart Centre Osnabrück / Bad Rothenfelde, Dept. of Cardiology and Angiology, D-49074, Osnabrück, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volker Ruppert
40Klinik für Innere Medizin-Kardiologie UKGM GmbH Standort Marburg Baldingerstrasse, Marburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luigi Tavazzi
41Maria Cecilia Hospital, GVM Care and Research, Cotignola, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Dubourg
42Université de Versailles-Saint Quentin, Hôpital Ambroise Paré, AP-HP, Boulogne, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerard Roizes
43Institut de Génétique Humaine, UPR 1142, CNRS, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Dorent
44Service de Cardiologie, CHU Tenon, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pascal DeGroote
45Service de Cardiologie, Hôpital Cardiologique, Lille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Fauchier
46Service de Cardiologie, Centre Hospitalier Universitaire Trousseau, Tours, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Noël Trochu
47INSERM UMR915, l’institut du thorax, Nantes, France
48CHU Nantes, Service de Cardiologie, Nantes, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-François Aupetit
49Département de pathologie cardiovasculaire, Hôpital Saint-Joseph-Saint-Luc, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marine Germain
50INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Uwe Völker
5Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany
6DZHK (German Centre for Cardiovascular Research), partnersite Greifswald, Greifswald, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hemerich Daiane
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ibticem Raji
51AP-HP, Département de génétique, Centre de Référence Maladies Cardiaques Héréditaires, Hôpital Pitié-Salpêtrière, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Delphine Bacq-Daian
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carole Proust
50INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristin Lehnert
6DZHK (German Centre for Cardiovascular Research), partnersite Greifswald, Greifswald, Germany
54Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renee Maas
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
4Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Olaso
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ganapathivarma Saripella
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
55SLU Bioinformatics Infrastructure (SLUBI), PlantLink, Department of Plant Breeding, Swedish University of Agricultural Sciences, Alnarp, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephan B. Felix
6DZHK (German Centre for Cardiovascular Research), partnersite Greifswald, Greifswald, Germany
54Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven Mc Ginn
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laëtitia Duboscq-Bidot
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
14APHP, Pitié-Salpêtrière Hospital, Cardiology Department, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alain van Mil
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
4Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Céline Besse
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Fontaine
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hélène Blanché
53Laboratory of Excellence GENMED (Medical Genomics)
56Centre d’Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brendan Keating
57Division of Transplantation, Departments of Surgery, University of Pennsylvania, Philadelphia, the United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pablo Garcia-Pavia
58Department of Cardiology, Hospital Univeersitario Puerta de Hierro, CIBERCV, Madrid, Spain
59Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angélique Curjol
51AP-HP, Département de génétique, Centre de Référence Maladies Cardiaques Héréditaires, Hôpital Pitié-Salpêtrière, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne Boland
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michel Komajda
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
60Cardiology Department, Groupe Hospitaler Paris Saint Joseph, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François Cambien
50INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-François Deleuze
52Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France
53Laboratory of Excellence GENMED (Medical Genomics)
56Centre d’Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcus Dörr
6DZHK (German Centre for Cardiovascular Research), partnersite Greifswald, Greifswald, Germany
54Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Folkert W Asselbergs
3Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
61Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom
62Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Villard
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
14APHP, Pitié-Salpêtrière Hospital, Cardiology Department, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David-Alexandre Trégouët
50INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philippe Charron
1Sorbonne Université, INSERM, UMR-S1166, research unit on cardiovascular disorders, metabolism and nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, F-75013, Paris, France
2ICAN Institute for Cardiometabolism and Nutrition, F-75013, Paris, France
14APHP, Pitié-Salpêtrière Hospital, Cardiology Department, Paris, France
51AP-HP, Département de génétique, Centre de Référence Maladies Cardiaques Héréditaires, Hôpital Pitié-Salpêtrière, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Philippe Charron
  • For correspondence: sophie.garnier@sorbonne-universite.fr philippe.charron@aphp.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

We present the results of the largest genome wide association study (GWAS) performed so far in dilated cardiomyopathy (DCM), a leading cause of systolic heart failure and cardiovascular death, with 2,719 cases and 4,440 controls in the discovery population. We identified and replicated two new DCM-associated loci, one on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication step, respectively) and the second on chromosome 22q11.23 (lead SNP rs7284877, p = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication step, respectively) while confirming two previously identified DCM loci on chromosome 10 and 1, BAG3 and HSPB7. The genetic risk score constructed from the number of lead risk-alleles at these four DCM loci revealed that individuals with 8 risk-alleles were at a 27% increased risk of DCM compared to individuals with 5 risk alleles (median of the referral population). We estimated the genome wide heritability at 31% ± 8%.

In silico annotation and functional 4C-sequencing analysis on iPSC-derived cardiomyocytes strongly suggest SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine and beta-alanine transporter whose involvement in myocardial dysfunction and DCM is supported by recent observations in humans and mice. Although less easy to discriminate the better candidate at the 22q11.23 locus, SMARCB1 appears as the strongest one.

This study provides both a better understanding of the genetic architecture of DCM and new knowledge on novel biological pathways underlying heart failure, with the potential for a therapeutic perspective.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted February 28, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23
Sophie Garnier, Magdalena Harakalova, Stefan Weiss, Michal Mokry, Vera Regitz-Zagrosek, Christian Hengstenberg, Thomas P Cappola, Richard Isnard, Eloisa Arbustini, Stuart A. Cook, Jessica van Setten, Jörg Callis, Hakon Hakonarson, Michael P Morley, Klaus Stark, Sanjay K. Prasad, Jin Li, Declan P O’Regan, Maurizia Grasso, Martina Müller-Nurasyid, Thomas Meitinger, Jean-Philippe Empana, Konstantin Strauch, Mélanie Waldenberger, Kenneth B Marguiles, Christine E. Seidman, Benjamin Meder, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Jeanette Erdman, Stefan Blankenberg, Thomas Wichter, Volker Ruppert, Luigi Tavazzi, Olivier Dubourg, Gerard Roizes, Richard Dorent, Pascal DeGroote, Laurent Fauchier, Jean-Noël Trochu, Jean-François Aupetit, Marine Germain, Uwe Völker, Hemerich Daiane, Ibticem Raji, Delphine Bacq-Daian, Carole Proust, Kristin Lehnert, Renee Maas, Robert Olaso, Ganapathivarma Saripella, Stephan B. Felix, Steven Mc Ginn, Laëtitia Duboscq-Bidot, Alain van Mil, Céline Besse, Vincent Fontaine, Hélène Blanché, Brendan Keating, Pablo Garcia-Pavia, Angélique Curjol, Anne Boland, Michel Komajda, François Cambien, Jean-François Deleuze, Marcus Dörr, Folkert W Asselbergs, Eric Villard, David-Alexandre Trégouët, Philippe Charron, On behalf of GENMED consortium
bioRxiv 2020.02.28.969147; doi: https://doi.org/10.1101/2020.02.28.969147
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23
Sophie Garnier, Magdalena Harakalova, Stefan Weiss, Michal Mokry, Vera Regitz-Zagrosek, Christian Hengstenberg, Thomas P Cappola, Richard Isnard, Eloisa Arbustini, Stuart A. Cook, Jessica van Setten, Jörg Callis, Hakon Hakonarson, Michael P Morley, Klaus Stark, Sanjay K. Prasad, Jin Li, Declan P O’Regan, Maurizia Grasso, Martina Müller-Nurasyid, Thomas Meitinger, Jean-Philippe Empana, Konstantin Strauch, Mélanie Waldenberger, Kenneth B Marguiles, Christine E. Seidman, Benjamin Meder, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Jeanette Erdman, Stefan Blankenberg, Thomas Wichter, Volker Ruppert, Luigi Tavazzi, Olivier Dubourg, Gerard Roizes, Richard Dorent, Pascal DeGroote, Laurent Fauchier, Jean-Noël Trochu, Jean-François Aupetit, Marine Germain, Uwe Völker, Hemerich Daiane, Ibticem Raji, Delphine Bacq-Daian, Carole Proust, Kristin Lehnert, Renee Maas, Robert Olaso, Ganapathivarma Saripella, Stephan B. Felix, Steven Mc Ginn, Laëtitia Duboscq-Bidot, Alain van Mil, Céline Besse, Vincent Fontaine, Hélène Blanché, Brendan Keating, Pablo Garcia-Pavia, Angélique Curjol, Anne Boland, Michel Komajda, François Cambien, Jean-François Deleuze, Marcus Dörr, Folkert W Asselbergs, Eric Villard, David-Alexandre Trégouët, Philippe Charron, On behalf of GENMED consortium
bioRxiv 2020.02.28.969147; doi: https://doi.org/10.1101/2020.02.28.969147

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4395)
  • Biochemistry (9619)
  • Bioengineering (7111)
  • Bioinformatics (24915)
  • Biophysics (12642)
  • Cancer Biology (9980)
  • Cell Biology (14388)
  • Clinical Trials (138)
  • Developmental Biology (7977)
  • Ecology (12135)
  • Epidemiology (2067)
  • Evolutionary Biology (16010)
  • Genetics (10938)
  • Genomics (14764)
  • Immunology (9889)
  • Microbiology (23719)
  • Molecular Biology (9493)
  • Neuroscience (50969)
  • Paleontology (370)
  • Pathology (1544)
  • Pharmacology and Toxicology (2688)
  • Physiology (4031)
  • Plant Biology (8685)
  • Scientific Communication and Education (1512)
  • Synthetic Biology (2403)
  • Systems Biology (6446)
  • Zoology (1346)