Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

Item Type:Article
Title:A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy
Creators Name:Meder, B. and Ruehle, F. and Weis, T. and Homuth, G. and Keller, A. and Franke, J. and Peil, B. and Bermejo, J.L. and Frese, K. and Huge, A. and Witten, A. and Vogel, B. and Haas, J. and Voelker, U. and Ernst, F. and Teumer, A. and Ehlermann, P. and Zugck, C. and Friedrichs, F. and Kroemer, H. and Doerr, M. and Hoffmann, W. and Maisch, B. and Pankuweit, S. and Ruppert, V. and Scheffold, T. and Kuehl, U. and Schultheiss, H.P. and Kreutz, R. and Ertl, G. and Angermann, C. and Charron, P. and Villard, E. and Gary, F. and Isnard, R. and Komajda, M. and Lutz, M. and Meitinger, T. and Sinner, M.F. and Wichmann, H.E. and Krawczak, M. and Ivandic, B. and Weichenhan, D. and Gelbrich, G. and El-Mokhtari, N.E. and Schreiber, S. and Felix, S.B. and Hasenfuß, G. and Pfeufer, A. and Huebner, N. and Kaeaeb, S. and Arbustini, E. and Rottbauer, W. and Frey, N. and Stoll, M. and Katus, H.A.
Abstract:Aims: 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. Methods and results: 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. Conclusion: 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.
Keywords:Dilated Cardiomyopathy, DCM, Genome-Wide Association Study
Source:European Heart Journal
ISSN:0195-668X
Publisher:Oxford University Press (U.K.)
Volume:35
Number:16
Page Range:1069-1077
Date:12 July 2013
Official Publication:https://doi.org/10.1093/eurheartj/eht251
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library