Guo, Dongchuan
Mayo Clinic
Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (D.G., D.M., D.R.M., S.K.P.).
Citations 2
Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve
Thériault, Sébastien , Holdcraft, Jacob A., Sharipova, Dinara , Dębiec, Radosław , Peloso, Gina M., Al‐Kassou, Baravan , Swan, Elena Ashikhmina , Ballotta, Andrea, Björck, Hanna M. , Braund, Peter S. , Corriveau, François, Dagenais, François, Francke, Michael, Gorbatov, Svetlana, Guo, Dongchuan, Habchi, Karam M, Scouarnec, Solena Le , Lichtner, Peter , Nguyen, Thy B., Norris, R., Pibarot, P, Simonet, Floriane, Tm, Sundt, Tessler, Idit , Willer, Cristen J., Wittmann, Susanne, Yang, Bo, Berezovets, Igor, Doppler, S. , Dreßen, Martina, Knoll, Katharina, Puehler, T., Schunkert, H, Bissell, Malenka M. , Bolger, Aidan, Brion, M, Citro, Rodolfo, Deeb, G. Michael, Corte, Alessandro Della, Dina, C., Eriksson, Per, Evangelista, Arturo , Franco-Cereceda, Anders, Gilon, Dan, Hetherington, Simon, Huggins, G S, Krane, Markus , Tourneau, Thierry Le, Limongelli, Giuseppe, Mathieu, P., Messika-Zeitoun, David, Michelena, Hector I., Milewicz, Dianna, Murdock, David R. , Nickenig, G., Nistri, Stefano, Nöthen, M, Samani, Nilesh J. , Schott, J., Webb, Tom R., Abdelilah-Seyfried, Salim, Schumacher, Johannes, Trenkwalder, Teresa , Body, Simon C. , Dina, Christian , Brión, Marı́a , Peloso, Gina M. , Webb, Tom R. , Faucherre, Adèle , Debiec, Radoslaw M , Peloso, Gina M , Al-Kassou, Baravan , Aranki, Sary , Ashikhmina Swan, Elena , Björck, Hanna M , Boureau, Anne Sophie , Braund, Peter S , Folkersen, Lasse , Guo, Dongchuan , Heydarpour, Mahyar , Isselbacher, Eric M , Jopling, Chris , Laporte, Fabien , Le Scouarnec, Solena , Li, Zhonglin , Lichtner, Peter , Maj, Carlo , Manikpurage, Hasanga D , Nguyen, Thy B , Norris, Russell A , Pibarot, Phillippe , Sarubbi, Berardo , Simonet, Floriane , Sundt, Thoralf , Surakka, Ida , Tessler, Idit , Yang, Bo , Doppler, Stefanie A , Dreßen, Martina , Knoll, Katharina , Puehler, Thomas , Schunkert, Heribert , Bissell, Malenka M , Bossé, Yohan , Bossone, Eduardo , Brion, María , Citro, Rodolfo , de Vincentiis, Carlo , Deeb, G Michael , Della Corte, Alessandro , Dina, Christian , Durst, Ronen , Ensminger, Stephan , Eriksson, Per , Evangelista, Arturo , Franco-Cereceda, Anders , Gilon, Dan , Giusti, Betti , Hetherington, Simon L , Huggins, Gordon S , Le Tourneau, Thierry , Limongelli, Giuseppe , Mathieu, Patrick , Messika-Zeitoun, David , Michelena, Hector I , Milewicz, Dianna M , Muehlschlegel, Jochen D , Murdock, David R , Nickenig, Georg , Nistri, Stefano , Nöthen, Markus M , Prakash, Siddharth K , Samani, Nilesh J , Jacques Schott, Jean , Webb, Tom R , Zaffran, Stéphane , Eagle, Kim , Body, Simon C , Holdcraft, Jacob A., Bellino, Michele , Dagenais, François, Forte, Amalia , Frigiola, Alessandro , Guo, Dongchuan , Isselbacher, Eric M. , Nelson, Christopher P. , Ong, Chin Siang , Roychowdhury, Tanmoy , Surakka, Ida , Willer, Cristen J , Aviérinos, Jean-François , Bolger, Aidan P. , Bossé, Yohan , Bossone, Eduardo , Citro, Rodolfo , Deeb, G. Michael , Corte, Alessandro Della , Gilon, Dan, Huggins, Gordon S. , Tourneau, Thierry Le , Mathieu, Patrick , Messika–Zeitoun, David , Nistri, Stefano , Nöthen, Markus M. , Pluchinotta, Francesca Romana , Prakash, Siddharth K. , Schott, Jean‐Jacques , Zaffran, Stéphane , Abdelilah‐Seyfried, Salim , Eagle, Kim A. , Schumacher, Johannes
Circulation | February 6, 2026 | Volume: 153 | Issue: 14 | Pages: 1060-1076
10.1161/circulationaha.125.074752
BACKGROUND: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV. METHODS: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified in zebrafish. A polygenic risk score was developed, its association with BAV was evaluated in an independent cohort, and its association with a wide range of phenotypes (n=976) was evaluated in UK Biobank (n=355 618 individuals). RESULTS: Thirty-six genomic loci were identified, including 32 that were not described previously. Among the prioritized genes, KANK2 and ERBB4 were identified as potentially causal through transcriptomic analyses, colocalization, and Mendelian randomization based on gene expression in human aortic valves (n=484), whereas PRDM6 and STRN were prioritized using similar analyses from aortic (n=326) and left ventricular tissues (n=326), respectively. Targeting 4 candidate genes ( WNT4 , LEF1 , STRN , and KANK2 ) in zebrafish led to disruption in cardiac development. A polygenic risk score was associated with an odds ratio of 2.07 (95% CI, 1.90–2.25; P =5.43×10 -62 ) per SD for BAV and significantly associated with thoracic aortic aneurysm and atrial fibrillation in UK Biobank. CONCLUSIONS: This study supports a significant polygenic contribution to BAV, where the combination of multiple common variants in genes involved in heart morphogenesis disrupts aortic valve development.
Bicuspid Aortic Valve Disease with Early-Onset Complications: Characteristics and Aortic Outcomes
Selbst, Maximilian A. , Svetgoff, Megan L., Sabaté-Rotés, Anna , Backer, Julie De , Mosquera, Laura Muiño , Yetman, Anji T. , Bissell, Malenka M. , Andreassi, Maria Grazia , Foffa, Ilenia , Hui, Dawn S. , Caffarelli, Anthony, Kim, Yuli Y. , Guo, Dongchuan , Citro, Rodolfo , Marco, Margot De , Tretter, Justin T. , Morris, Shaine A. , Body, Simon C. , Prakash, Siddharth K. , Morris, Shaine A , Prakash, Siddharth K , Bissell, Malenka M , Body, Simon C , Citro, Rodolfo , De Backer, Julie F A , Kim, Yuli Y , Muiño-Mosquera, Laura , Guo, Dongchuan , Laughlin, Megan K., Ward, Colin R. , Michelena, Héctor I. , Bianco, Lisa , Yetman, Anji T., Bissell, Malenka M, Andreassi, Maria Grazia, Caffarelli, Anthony, Dongchuan, Guo, Tretter, Justin T., McBride, Kim L. , Investigators, EBAV
Hearts | June 21, 2024 | Volume: 5 | Issue: 3 | Pages: 253-258
Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults, but it can also cause childhood-onset complications. The presentation and clinical course of young adults who present due to BAV complications are relatively uncharacterized. In a multicenter study, we found that young people who experience significant complications related to BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early-onset BAV complications.