Genetic susceptibility in Takotsubo syndrome: a candidate gene association analysis in the French TAKOGENE cohort
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.
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BibTeX
@article{nicolas2026genetic,
title = {{Genetic susceptibility in Takotsubo syndrome: a candidate gene association analysis in the French TAKOGENE cohort}},
author = {Laury Nicolas and Sophie Garnier and Edouard Gerbaud and Franck Paganelli and Denis Doyen and Pascal Motreff and Patrick Meimoun and Erwan Donal and Vincent Probst and Grégory Ducrocq and Jean-François Aupetit and Ariel Cohen and Christophe Tribouilloy and Olivier Nallet and Nicolas Lamblin and Damien Logeart and Frédéric Moulin and Eric Durand and Olivier Varenne and Pascal Lim and Taing Lieng and Robert Olaso and Doris Lechner and Jean-François Deleuze and Philippe Charron and Nicolas Mansencal},
journal = {European Journal of Medical Genetics},
year = {2026},
month = oct,
doi = {10.1016/j.ejmg.2026.105108},
url = {https://u-picardie.hal.science/hal-05801578v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Genetic susceptibility in Takotsubo syndrome: a candidate gene association analysis in the French TAKOGENE cohort
AU - Laury Nicolas
AU - Sophie Garnier
AU - Edouard Gerbaud
AU - Franck Paganelli
AU - Denis Doyen
AU - Pascal Motreff
AU - Patrick Meimoun
AU - Erwan Donal
AU - Vincent Probst
AU - Grégory Ducrocq
AU - Jean-François Aupetit
AU - Ariel Cohen
AU - Christophe Tribouilloy
AU - Olivier Nallet
AU - Nicolas Lamblin
AU - Damien Logeart
AU - Frédéric Moulin
AU - Eric Durand
AU - Olivier Varenne
AU - Pascal Lim
AU - Taing Lieng
AU - Robert Olaso
AU - Doris Lechner
AU - Jean-François Deleuze
AU - Philippe Charron
AU - Nicolas Mansencal
PY - 2026
DA - 2026/10/15
JO - European Journal of Medical Genetics
DO - 10.1016/j.ejmg.2026.105108
UR - https://u-picardie.hal.science/hal-05801578v1
AB - 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.
SN - 1769-7212
ER -