Genome wide association analysis in dilated cardiomyopathy revealed two new susceptibility loci for systolic heart failure - CEA - Commissariat à l’énergie atomique et aux énergies alternatives Accéder directement au contenu
Article Dans Une Revue European Journal of Human Genetics Année : 2020

Genome wide association analysis in dilated cardiomyopathy revealed two new susceptibility loci for systolic heart failure

Résumé

We conducted the largest Genome Wide Association Study performed so far in Dilated Cardiomyopathy (DCM), a leading cause of systolic heart failure and cardiovascular death. Using a discovery phase of 2,719 cases and 4,440 controls and a replication phase of 584 independent cases and 966 controls, we identified and replicated two new DCM-associated loci one on chromosome 3p (meta-analysis p = 5.3 10−13) and the second on chromosome 22q (meta-analysis p = 5.0 10−10) while confirming the two previously identified DCM loci on chromosome 10 and 1, BAG3 and HSPB7 for an estimated heritability of 31% ± 8%. The genetic risk score constructed from the number of lead risk-alleles at these 4 loci revealed a 27% risk increased in individuals with 8 risk-alleles compared to the 5 risk alleles reference group. The two association signals were then fine-mapped by combining in silico and functional genomics investigations. While a few genes remain candidates at the second locus and deserve further investigations, our work clearly identified one gene as responsible for the association at the first locus whose role in the pathophysiology of DCM is supported by recent observations in human and mice. As the biological pathway in which this gene is involved is a potential target for pharmacological agents, our finding opens novel therapeutic perspectives for treating or preventing heart failure. These results provide new findings that add both on the understanding of the genetic architecture of heart failure and on potential new players involved in the pathophysiology of this devastating disease.
Fichier non déposé

Dates et versions

cea-04419430 , version 1 (26-01-2024)

Identifiants

  • HAL Id : cea-04419430 , version 1

Citer

S. Garnier, M. Harakalova, S. Weiss, M. Mokry, J. Van Setten, et al.. Genome wide association analysis in dilated cardiomyopathy revealed two new susceptibility loci for systolic heart failure. European Journal of Human Genetics, 2020, 28 (Suppl 1), pp.266-267. ⟨cea-04419430⟩
10 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More