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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.P.* ; 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.-E. ; Krawczak, M.* ; Ivandic, B.* ; Weichenhan, D.* ; Gelbrich, G.* ; El-Mokhtari, N.E.* ; Schreiber, S.* ; Felix, S.B.* ; Hasenfuß, G.* ; Pfeufer, A. ; Hubner, N.* ; Kääb, S.* ; Arbustini, E.* ; Rottbauer, W.* ; Frey, N.* ; Stoll, M.* ; Katus, H.A.*

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

Eur. Heart J. 35, 1069-1077 (2014)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.  
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter DCM; Dilated cardiomyopathy; Genome-wide association study; Coronary-artery-disease; Heart-failure; Hla-c; Susceptibility Loci; Myocarditis; Cardiology; Variants; Society; Health; Gene
Sprache englisch
Veröffentlichungsjahr 2014
Prepublished im Jahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Zeitschrift European Heart Journal
Quellenangaben Band: 35, Heft: 16, Seiten: 1069-1077 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute of Bioinformatics and Systems Biology (IBIS)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health

30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er) Genetics and Epidemiology

Enabling and Novel Technologies
PSP-Element(e) G-500700-001
G-503900-002
G-503700-001
PubMed ID 23853074
DOI 10.1093/eurheartj/eht251
WOS ID WOS:000335813500015
Scopus ID 84899538064
Erfassungsdatum 2013-12-31
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