A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy. Meder, B., Rühle, F., Weis, T., Homuth, G., Keller, A., Franke, J., Peil, B., Lorenzo Bermejo, J., Frese, K., Huge, A., Witten, A., Vogel, B., Haas, J., Völker, U., Ernst, F., Teumer, A., Ehlermann, P., Zugck, C., Friedrichs, F., Kroemer, H., Dörr, M., Hoffmann, W., Maisch, B., Pankuweit, S., Ruppert, V., Scheffold, T., Kühl, U., Schultheiss, H., Kreutz, R., Ertl, G., Angermann, C., Charron, P., Villard, E., Gary, F., Isnard, R., Komajda, M., Lutz, M., Meitinger, T., Sinner, M. F, Wichmann, H., Krawczak, M., Ivandic, B., Weichenhan, D., Gelbrich, G., El-Mokhtari, N., Schreiber, S., Felix, S. B, Hasenfuß, G., Pfeufer, A., Hübner, N., Kääb, S., Arbustini, E., Rottbauer, W., Frey, N., Stoll, M., & Katus, H. A European heart journal, 35:1069–1077, April, 2014.
doi abstract bibtex

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.

@Article{Meder2014,
  author          = {Meder, Benjamin and Rühle, Frank and Weis, Tanja and Homuth, Georg and Keller, Andreas and Franke, Jennifer and Peil, Barbara and Lorenzo Bermejo, Justo and Frese, Karen and Huge, Andreas and Witten, Anika and Vogel, Britta and Haas, Jan and Völker, Uwe and Ernst, Florian and Teumer, Alexander and Ehlermann, Philipp and Zugck, Christian and Friedrichs, Frauke and Kroemer, Heyo and Dörr, Marcus and Hoffmann, Wolfgang and Maisch, Bernhard and Pankuweit, Sabine and Ruppert, Volker and Scheffold, Thomas and Kühl, Uwe and Schultheiss, Hans-Peter and Kreutz, Reinhold and Ertl, Georg and Angermann, Christiane and Charron, Philippe and Villard, Eric and Gary, Françoise and Isnard, Richard and Komajda, Michel and Lutz, Matthias and Meitinger, Thomas and Sinner, Moritz F and Wichmann, H-Erich and Krawczak, Michael and Ivandic, Boris and Weichenhan, Dieter and Gelbrich, Goetz and El-Mokhtari, Nour-Eddine and Schreiber, Stefan and Felix, Stephan B and Hasenfuß, Gerd and Pfeufer, Arne and Hübner, Norbert and Kääb, Stefan and Arbustini, Eloisa and Rottbauer, Wolfgang and Frey, Norbert and Stoll, Monika and Katus, Hugo A},
  title           = {A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.},
  journal         = {European heart journal},
  year            = {2014},
  volume          = {35},
  pages           = {1069--1077},
  month           = apr,
  issn            = {1522-9645},
  abstract        = {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.},
  chemicals       = {HLA-C Antigens},
  citation-subset = {IM},
  completed       = {2014-12-16},
  country         = {England},
  doi             = {10.1093/eurheartj/eht251},
  issn-linking    = {0195-668X},
  issue           = {16},
  keywords        = {Cardiomyopathy, Dilated, genetics, physiopathology; Case-Control Studies; Chromosomes, Human, Pair 6, genetics; Female; Genetic Predisposition to Disease, genetics; Genome-Wide Association Study; Genotype; HLA-C Antigens, genetics; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide, genetics; Stroke Volume, physiology; DCM; Dilated cardiomyopathy; Genome-wide association study},
  nlm-id          = {8006263},
  owner           = {NLM},
  pii             = {eht251},
  pmid            = {23853074},
  pubmodel        = {Print-Electronic},
  pubstatus       = {ppublish},
  revised         = {2014-04-22},
}

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