A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human
Tekijät: Niskanen Julia E.; Ohlsson Åsa; Ljungvall Ingrid; Drögemüller Michaela; Ernst Robert F.; Dooijes Dennis; van Deutekom Hanneke W. M.; van Tintelen J. Peter; Snijders Blok Christian J. B.; van Vugt Marion; van Setten Jessica; Asselbergs Folkert W.; Petrič Aleksandra Domanjko; Salonen Milla; Hundi Sruthi; Hörtenhuber Matthias; {name=DoGA consortium, sequence=additional, affiliation=[]}; Daub Carsten; Araujo César L.; Quintero Ileana B.; Kyöstilä Kaisa; Kaukonen Maria; Arumilli Meharji; Sarviaho Riika; Puurunen Jenni; Sulkama Sini; Karjalainen Sini; Sukura Antti; Syrjä Pernilla; Airas Niina; Pekkarinen Henna; Kareinen Ilona; Javela Hanna-Maaria; Knuuttila Anna; Nordgren Heli; Hagner Karoliina; Pääkkönen Tarja; Iivanainen Antti; Krjutskov Kaarel; Ezer Sini; Saarinen Auli; Katayama Shintaro; Yoshihara Masahito; Mukarram Abdul Kadir; Aljelaify Rasha Fahad; Ross Fiona; Raman Amitha; Stevens Irene; Gusev Oleg; Bannasch Danika; Schoenebeck Jeffrey J.; Kere Juha; Pyle W. Glen; Donner Jonas; Postma Alex V.; Leeb Tosso; Andersson Göran; Hytönen Marjo K.; Häggström Jens; Wiberg Maria; Friederich Jana; Eberhard Jenny; Harakalova Magdalena; van Steenbeek Frank G.; Wess Gerhard; Lohi Hannes
Kustantaja: Springer Science and Business Media LLC
Julkaisuvuosi: 2023
Journal: Genome Medicine
Tietokannassa oleva lehden nimi: Genome Medicine
Artikkelin numero: 73
Vuosikerta: 15
Numero: 1
eISSN: 1756-994X
DOI: https://doi.org/10.1186/s13073-023-01221-3
Verkko-osoite: https://doi.org/10.1186/s13073-023-01221-3
BackgroundDilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.MethodsWe performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.ResultsOur results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.ConclusionsCollectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.
