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; Cristen J. Willer

doi:10.1038/ncomms15481

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 DubéEric 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, Cristen J. Willer

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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
DOIs	https://doi.org/10.1038/ncomms15481
State	Published - 25 May 2017

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Yang, B., Zhou, W., Jiao, J., Nielsen, J. B., Mathis, M. R., Heydarpour, M., Lettre, G., Folkersen, L., 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{55211ffd557e446590f3aeeaf676302e,

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 Zhou and Jiao Jiao and Nielsen, {Jonas B.} and Mathis, {Michael R.} and Mahyar Heydarpour and Guillaume Lettre and Lasse Folkersen 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 Dub{\'e}, {Marie Pierre} and Isselbacher, {Eric M.} and Anders Franco-Cereceda and Guo, {Dong Chuan} 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 Gon{\c c}alo Abecasis and Eagle, {Kim A.} and Boyle, {Alan P.} and Loos, {Ruth J.F.} and Per Eriksson and Tardif, {Jean Claude} and Brummett, {Chad M.} and Milewicz, {Dianna M.} and Body, {Simon C.} and Willer, {Cristen J.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

month = may,

day = "25",

doi = "10.1038/ncomms15481",

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Yang, B, Zhou, W, Jiao, J, Nielsen, JB, Mathis, MR, Heydarpour, M, Lettre, G, Folkersen, L, Prakash, S, Schurmann, C, Fritsche, L, Farnum, GA, Lin, M, Othman, M, Hornsby, W, Driscoll, A, Levasseur, A, Thomas, M, Farhat, L, Dubé, MP, Isselbacher, EM, Franco-Cereceda, A, Guo, DC, 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, JC, 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

AU - Jiao, Jiao

AU - Nielsen, Jonas B.

AU - Mathis, Michael R.

AU - Heydarpour, Mahyar

AU - Lettre, Guillaume

AU - Folkersen, Lasse

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 - Dubé, 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, Gonçalo

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 - 2017/5/25

Y1 - 2017/5/25

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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.

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U2 - 10.1038/ncomms15481

DO - 10.1038/ncomms15481

M3 - Article

C2 - 28541271

AN - SCOPUS:85019653719

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

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