Meder, Benjamin; Rühle, Frank; Weis, Tanja; Homuth, Georg; Keller, Andreas; Franke, Jennifer; Peil, Barbara; Lorenzo Bermejo, Justo; Frese, Karen; Huge, Andreas; Witten, Anika; Vogel, Britta; Haas, Jan; Völker, Uwe; Ernst, Florian; Teumer, Alexander; Ehlermann, Philipp; Zugck, Christian; Friedrichs, Frauke; Kroemer, Heyo; Dörr, Marcus; Hoffmann, Wolfgang; Maisch, Bernhard; Pankuweit, Sabine; Ruppert, Volker; Scheffold, Thomas; Kühl, Uwe; Schultheiss, Hans-Peter; Kreutz, Reinhold; Ertl, Georg; Angermann, Christiane; Charron, Philippe; Villard, Eric; Gary, Françoise; Isnard, Richard; Komajda, Michel; Lutz, Matthias; Meitinger, Thomas; Sinner, Moritz F; Wichmann, H-Erich; Krawczak, Michael; Ivandic, Boris; Weichenhan, Dieter; Gelbrich, Goetz; El-Mokhtari, Nour-Eddine; Schreiber, Stefan; Felix, Stephan B; Hasenfuß, Gerd; Pfeufer, Arne; Hübner, Norbert; Kääb, Stefan; Arbustini, Eloisa; Rottbauer, Wolfgang; Frey, Norbert; Stoll, Monika; Katus, Hugo A     «

Meder, Benjamin; Rühle, Frank; Weis, Tanja; Homuth, Georg; Keller, Andreas; Franke, Jennifer; Peil, Barbara; Lorenzo Bermejo, Justo; Frese, Karen; Huge, Andreas; Witten, Anika; Vogel, Britta; Haas, Jan; Völker, Uwe; Ernst, Florian; Teumer, Alexander; Ehlermann, Philipp; Zugck, Christian; Friedrichs, Frauke; Kroemer, Heyo; Dörr, Marcus; Hoffmann, Wolfgang; Maisch, Bernhard; Pankuweit, Sabine; Ruppert, Volker; Scheffold, Thomas; Kühl, Uwe; Schultheiss, Hans-Peter; Kreutz, Reinhold; Ertl, Georg; An...     »

Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM.Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors.The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.     «

Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM.Applying a three-staged study desig...     »