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

Bo Yang; Wei-Wu Zhou; Jiao Jiao; Jonas B. Nielsen; Michael R. Mathis; Mahyar Heydarpour; Guillaume Lettre; Lasse Westergaard 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 Dube; 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; Goncalo 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; Cristen J. Willer

doi:10.1038/ncomms15481

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

Bo Yang, Wei-Wu Zhou, Jiao Jiao, Jonas B. Nielsen, Michael R. Mathis, Mahyar Heydarpour, Guillaume Lettre, Lasse Westergaard 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 DubeEric 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, Goncalo 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, Cristen J. Willer

Research output: Contribution to journal › Journal article › Research › peer-review

283 Downloads (Pure)

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.

Original language	English
Article number	15481
Journal	Nature Communications
Volume	8
Number of pages	10
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms15481
Publication status	Published - 2017

Access to Document

10.1038/ncomms15481

55Final published version, 1 MB

OpenUrl availability

Full text

Cite this

Yang, B., Zhou, W.-W., Jiao, J., Nielsen, J. B., Mathis, M. R., Heydarpour, M., Lettre, G., Folkersen, L. W., Prakash, S., Schurmann, C., Fritsche, L., Farnum, G. A., Lin, M., Othman, M., Hornsby, W., Driscoll, A., Levasseur, A., Thomas, M., Farhat, L., ... Willer, C. J. (2017). Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nature Communications, 8, Article 15481. https://doi.org/10.1038/ncomms15481

@article{33ae50514fc9466b81d17df4039df538,

title = "Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve",

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.",

author = "Bo Yang and Wei-Wu Zhou and Jiao Jiao and Nielsen, {Jonas B.} and Mathis, {Michael R.} and Mahyar Heydarpour and Guillaume Lettre and Folkersen, {Lasse Westergaard} and Siddharth Prakash and Claudia Schurmann and Lars Fritsche and Farnum, {Gregory A.} and Maoxuan Lin and Mohammad Othman and Whitney Hornsby and Anisa Driscoll and Alexandra Levasseur and Marc Thomas and Linda Farhat and Marie-Pierre Dube and Isselbacher, {Eric M.} and Anders Franco-Cereceda and Dong-Chuan Guo and Bottinger, {Erwin P.} and Deeb, {G. Michael} and Anna Booher and Sachin Kheterpal and Chen, {Y. Eugene} and Kang, {Hyun Min} and Jacob Kitzman and Cordell, {Heather J.} and Keavney, {Bernard D.} and Goodship, {Judith A.} and Ganesh, {Santhi K.} and Goncalo Abecasis and Eagle, {Kim A.} and Boyle, {Alan P.} and Loos, {Ruth J. F.} and Per Eriksson and Jean-Claude Tardif and Brummett, {Chad M.} and Milewicz, {Dianna M.} and Body, {Simon C.} and Willer, {Cristen J.}",

year = "2017",

doi = "10.1038/ncomms15481",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Yang, B, Zhou, W-W, Jiao, J, Nielsen, JB, Mathis, MR, Heydarpour, M, Lettre, G, Folkersen, LW, Prakash, S, Schurmann, C, Fritsche, L, Farnum, GA, Lin, M, Othman, M, Hornsby, W, Driscoll, A, Levasseur, A, Thomas, M, Farhat, L, Dube, M-P, Isselbacher, EM, Franco-Cereceda, A, Guo, D-C, Bottinger, EP, Deeb, GM, Booher, A, Kheterpal, S, Chen, YE, Kang, HM, Kitzman, J, Cordell, HJ, Keavney, BD, Goodship, JA, Ganesh, SK, Abecasis, G, Eagle, KA, Boyle, AP, Loos, RJF, Eriksson, P, Tardif, J-C, Brummett, CM, Milewicz, DM, Body, SC & Willer, CJ 2017, 'Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve', Nature Communications, vol. 8, 15481. https://doi.org/10.1038/ncomms15481

TY - JOUR

T1 - Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

AU - Yang, Bo

AU - Zhou, Wei-Wu

AU - Jiao, Jiao

AU - Nielsen, Jonas B.

AU - Mathis, Michael R.

AU - Heydarpour, Mahyar

AU - Lettre, Guillaume

AU - Folkersen, Lasse Westergaard

AU - Prakash, Siddharth

AU - Schurmann, Claudia

AU - Fritsche, Lars

AU - Farnum, Gregory A.

AU - Lin, Maoxuan

AU - Othman, Mohammad

AU - Hornsby, Whitney

AU - Driscoll, Anisa

AU - Levasseur, Alexandra

AU - Thomas, Marc

AU - Farhat, Linda

AU - Dube, Marie-Pierre

AU - Isselbacher, Eric M.

AU - Franco-Cereceda, Anders

AU - Guo, Dong-Chuan

AU - Bottinger, Erwin P.

AU - Deeb, G. Michael

AU - Booher, Anna

AU - Kheterpal, Sachin

AU - Chen, Y. Eugene

AU - Kang, Hyun Min

AU - Kitzman, Jacob

AU - Cordell, Heather J.

AU - Keavney, Bernard D.

AU - Goodship, Judith A.

AU - Ganesh, Santhi K.

AU - Abecasis, Goncalo

AU - Eagle, Kim A.

AU - Boyle, Alan P.

AU - Loos, Ruth J. F.

AU - Eriksson, Per

AU - Tardif, Jean-Claude

AU - Brummett, Chad M.

AU - Milewicz, Dianna M.

AU - Body, Simon C.

AU - Willer, Cristen J.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms15481

DO - 10.1038/ncomms15481

M3 - Journal article

C2 - 28541271

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15481

ER -

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

Abstract

Access to Document

OpenUrl availability

Fingerprint

Cite this