Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

Bo Yang (), Wei Zhou, Jiao Jiao, Jonas B. Nielsen, Michael R. Mathis, Mahyar Heydarpour, Guillaume Lettre, Lasse Folkersen, Siddharth Prakash, Claudia Schurmann, Lars Fritsche, Gregory A. Farnum, Maoxuan Lin, Mohammad Othman, Whitney Hornsby, Anisa Driscoll, Alexandra Levasseur, Marc Thomas, Linda Farhat, Marie-Pierre Dubé, Eric M. Isselbacher, Anders Franco-Cereceda, Dong-chuan Guo, Erwin P. Bottinger, G. Michael Deeb, Anna Booher, Sachin Kheterpal, Y. Eugene Chen, Hyun Min Kang, Jacob Kitzman, Heather J. Cordell, Bernard D. Keavney, Judith A. Goodship, Santhi K. Ganesh, Gonçalo Abecasis, Kim A. Eagle, Alan P. Boyle, Ruth J. F. Loos, Per Eriksson, Jean-Claude Tardif, Chad M. Brummett, Dianna M. Milewicz, Simon C. Body and Cristen J. Willer ()
Additional contact information
Bo Yang: University of Michigan
Wei Zhou: University of Michigan
Jiao Jiao: University of Michigan
Jonas B. Nielsen: University of Michigan
Michael R. Mathis: University of Michigan
Mahyar Heydarpour: Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
Guillaume Lettre: Montreal Heart Institute
Lasse Folkersen: Cardiovascular Medicine Unit, Center for Molecular Medicine, Karolinska University Hospital Solna, Karolinska Institutet
Siddharth Prakash: University of Texas Health Science Center at Houston McGovern Medical School
Claudia Schurmann: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
Lars Fritsche: University of Michigan
Gregory A. Farnum: University of Michigan
Maoxuan Lin: University of Michigan
Mohammad Othman: University of Michigan
Whitney Hornsby: Frankel Cardiovascular Center, University of Michigan
Anisa Driscoll: Frankel Cardiovascular Center, University of Michigan
Alexandra Levasseur: Frankel Cardiovascular Center, University of Michigan
Marc Thomas: Frankel Cardiovascular Center, University of Michigan
Linda Farhat: Frankel Cardiovascular Center, University of Michigan
Marie-Pierre Dubé: Montreal Heart Institute
Eric M. Isselbacher: Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
Anders Franco-Cereceda: Cardiothoracic Surgery Unit, Karolinska University Hospital Solna, Karolinska Institutet
Dong-chuan Guo: University of Texas Health Science Center at Houston McGovern Medical School
Erwin P. Bottinger: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
G. Michael Deeb: University of Michigan
Anna Booher: Frankel Cardiovascular Center, University of Michigan
Sachin Kheterpal: University of Michigan
Y. Eugene Chen: University of Michigan
Hyun Min Kang: University of Michigan
Jacob Kitzman: University of Michigan
Heather J. Cordell: Institute of Genetic Medicine, Newcastle University
Bernard D. Keavney: Faculty of Biology, Medicine and Health, The University of Manchester
Judith A. Goodship: Institute of Genetic Medicine, Newcastle University
Santhi K. Ganesh: Frankel Cardiovascular Center, University of Michigan
Gonçalo Abecasis: University of Michigan
Kim A. Eagle: Frankel Cardiovascular Center, University of Michigan
Alan P. Boyle: University of Michigan
Ruth J. F. Loos: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
Per Eriksson: Cardiovascular Medicine Unit, Center for Molecular Medicine, Karolinska University Hospital Solna, Karolinska Institutet
Jean-Claude Tardif: Montreal Heart Institute
Chad M. Brummett: University of Michigan
Dianna M. Milewicz: University of Texas Health Science Center at Houston McGovern Medical School
Simon C. Body: Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
Cristen J. Willer: Frankel Cardiovascular Center, University of Michigan

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms15481 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15481

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15481

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().