Genetic susceptibility in Takotsubo syndrome: a candidate gene association analysis in the French TAKOGENE cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT Takotsubo syndrome (TTS) is a stress-induced left ventricular (LV) cardiomyopathy with an unclear genetic predisposition. We investigated whether single nucleotide polymorphisms (SNPs) previously associated with other cardiomyopathies or LV physiological traits contribute to TTS susceptibility. We conducted a case-control study based on the French multicentre TAKOGENE study (NCT01520610), including 261 unrelated TTS patients and 259 sex- and age-matched controls presenting with acute coronary syndrome. All participants were of European ancestry. A total of 325 SNPs were selected from large-scale genome-wide association studies of cardiomyopathies (n=202) and LV structural/functional traits (n=123), derived from polygenic risk scores. Genotyping was performed using the Infinium OmniExpressExome-8 array. Associations were assessed by logistic regression under an additive model, adjusted for age and sex, with group-specific Bonferroni correction. A sensitivity analysis compared the 261 TTS cases with 973 French population controls from the EPP3 cohort. After quality control and statistical analysis, seventeen SNPs (nine related to cardiomyopathies and eight to LV traits) showed nominal associations (P < 0.05), but none remained significant after group-specific Bonferroni correction. The strongest signal was observed for rs6885658 in the CPEB4 gene (OR 1.62, 95% CI 1.23–2.15; P = 5.8 × 10 -4 ) related to cardiomyopathy traits. The EPP3 population-control sensitivity analysis was consistent with the primary analysis, with no association remaining significant after correction. In conclusion, common genetic variants previously associated with cardiomyopathies or LV traits do not appear to have a major effect on TTS risk. These findings support a disease-specific polygenic architecture of TTS, distinct from that underlying chronic cardiomyopathies and baseline LV traits. Future studies should explore alternative approaches, such as pathway-based analyses focusing on stress-response mechanisms.
Authors: Laury Nicolas, Sophie Garnier, Edouard Gerbaud, Franck Paganelli, Denis Doyen, Pascal Motreff, Patrick Meimoun, Erwan Donal, Vincent Probst, Grégory Ducrocq, Jean-François Aupetit, Ariel Cohen, Christophe Tribouilloy, Olivier Nallet, Nicolas Lamblin, Damien Logeart, Frédéric Moulin, Eric Durand, Olivier Varenne, Pascal Lim, Taing Lieng, Robert Olaso, Doris Lechner, Jean-François Deleuze, Philippe Charron, Nicolas Mansencal
Institutions: Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Centre Hospitalier Universitaire Pointe-à-Pitre, Université des Antilles, Inserm, Sorbonne Université, Unité de recherche sur les maladies cardiovasculaires et métaboliques, Fondation pour l’innovation en Cadiométabolisme et Nutrition, Hôpital Cardiologique du Haut-Lévêque, Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Hôpital Pasteur, Université Clermont Auvergne, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre Hospitalier Compiègne-Noyon, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Nantes, Institut du Thorax, Hôpital Bichat-Claude-Bernard, Centre Hospitalier Saint-Joseph Saint-Luc, Hôpital Saint-Antoine, Centre Hospitalier Universitaire Amiens-Picardie, Groupe Hospitalier Intercommunal Le Raincy Montfermeil, Hôpital Lariboisière, Centre Hospitalier Régional et Universitaire de Nancy, Hôpital Européen Georges-Pompidou, Hôpital Cochin, Hôpitaux Universitaires Henri-Mondor, Centre National de la Recherche Scientifique, Institut Pasteur, Université Paris Cité, Biologie du Développement et Cellules Souches, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Centre National de Recherche en Génomique Humaine, CEA Paris-Saclay, Fondation Jean Dausset-CEPH, Hôpital Ambroise-Paré, Université de Versailles Saint-Quentin-en-Yvelines, Centre de recherche en Epidémiologie et Santé des Populations
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,330
OpenAlex ID: W7221564916