Eriksson, Per
Mayo Clinic
Division of Cardiology, Center for Molecular Medicine, Department of Medicine (H.M.B., P.E.), Karolinska Institutet, Stockholm, Sweden.
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.
Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
Hof, Femke N. G. van ’t, Ruigrok, Ynte M. , Lee, Cue Hyunkyu , Ripke, Stephan , Anderson, Graig, Baas, Annette F., Blankensteijn, Jan D. , Böttinger, Erwin P. , Bown, Matthew J. , Broderick, Joseph P., Bijlenga, Philippe , Crosslin, David R. , Ebeling, Christian , Eriksson, Johan G. , Fornage, Myriam , Foroud, Tatiana, Fraunberg, Mikael von und zu , Friedrich, Christoph M. , Gaál, Emília Ilona, Gottesman, Omri, Guo, Dongchuan , Harrison, Seamus C. , Hernesniemi, Juha , Hofman, Albert , Inoue, Ituro , Jääskeläinen, Juha E. , Kiemeney, Lambertus A. , Kivisaari, Riku , Ko, Nerissa , Koskinen, Seppo, Kubo, Michiaki , Kuivaniemi, Helena , Laakso, Aki , Lehto, Hanna, LeMaire, Scott A. , Malinowski, Jennifer , McCarty, Catherine A. , Mosley, Thomas H., Nakaoka, Hirofumi , Peissig, Peggy , Pera, Joanna , Rasmussen‐Torvik, Laura J. , Ritchie, Marylyn D. , Rivadeneira, Fernando , Rij, André M. van , Santos‐Cortez, Regie Lyn P., Saratzis, Athanasios , Słowik, Agnieszka , Tromp, Gerard , Uitterlinden, André G. , Vermeulen, Sita H. , Wang, Gao T., Han, Buhm , Bakker, Paul I. W. de , Verissimo, Ana Raquel, Wright, Benjamin J., Bumpstead, Suzannah, Grétarsdóttir, Sólveig , Badger, Stephen A., Child, Anne H. , Cockerill, Gillian, Hafez, Hany , Futers, Simon , Sohrabi, Soroush, Smith, Alberto, Thompson, Matthew M., Bockxmeer, Frank M. van, Matthíasson, Stefán E., Þorsteinsdóttir, Unnur , Graaf, Jacqueline de , Palmen, Jutta, Lindholt, Jes S. , Bradley, Declan , Waltham, Matthew, Gwilliam, Rhian, Golledge, Jonathan , Eriksson, Per , Stefánsson, Kāri , Thompson, John R., Humphries, Steve E. , Sayers, Robert D., Deloukas, Panos , Samani, Nilesh J. , Phillip, L. Victoria, Hill, Geraldine B., Williams, Michael , Thomson, Ian , Krysa, Jo, Wilkins, Gerard , Vasudevan, Thodor M., Lewis, David R. , Blair, Ross D., Hill, Andrew A., de Andrade, Mariza, Ripke, Stephan , Andrade, Mariza de , Broderick, Joseph, Carrell, David , Crawford, Dana C. , Jones, Gregory T. , Kullo, Iftikhar J. , Kurki, Mitja , Lai, Dongbing , Leal, Suzanne M. , Low, Siew‐Kee , Milewicz, Dianna M. , Nakamura, Yusuke , Niemela, Mika R. , Pacheco, Jennifer A. , Takahashi, Atsushi , Verma, Shefali S. , Rinkel, Gabriël J.E. , Clough, Rachel E. , Scott, D. Julian A., Þorleifsson, Guðmar , Teijink, Joep A.W. , Wijmenga, Cisca , Smith, Andrew J P , Edkins, Sarah , Hunt, Sarah E , Potter, Simon , Norman, Paul E , Powell, Janet T. , Merriman, Tony Raymond , Kiemeney, Lambertus A , Bijlenga, Philippe , Lindholt, Jes Sanddal , Malinowski, Jennnifer , Rasmussen-Torvik, Laura J , Eriksson, Per
Journal of the American Heart Association | July 15, 2016 | Volume: 5 | Issue: 7 | Pages: No page available
Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.