Teumer, Alexander and Trenkwalder, Teresa and Kessler, Thorsten and Jamshidi, Yalda and van den Berg, Marten E. and Kaess, Bernhard and Nelson, Christopher P. and Bastiaenen, Rachel and De Bortoli, Marzia and Rossini, Alessandra and Deisenhofer, Isabel and Stark, Klaus and Assa, Solmaz and Braund, Peter S. and Cabrera, Claudia and Dominiczak, Anna F. and Gogele, Martin and Hall, Leanne M. and Ikram, M. Arfan and Kavousi, Maryam and Lackner, Karl J. and Mueller, Christian and Muenzel, Thomas and Nauck, Matthias and Padmanabhan, Sandosh and Pfeiffer, Norbert and Spector, Tim D. and Uitterlinden, Andre G. and Verweij, Niek and Voelker, Uwe and Warren, Helen R. and Zafar, Mobeen and Felix, Stephan B. and Kors, Jan A. and Snieder, Harold and Munroe, Patricia B. and Pattaro, Cristian and Fuchsberger, Christian and Schmidt, Georg and Nolte, Ilja M. and Schunkert, Heribert and Pramstaller, Peter P. and Wild, Philipp S. and van Der Harst, Pim and Stricker, Bruno H. and Schnabel, Renate B. and Samani, Nilesh J. and Hengstenberg, Christian and Doerr, Marcus and Behr, Elijah R. and Reinhard, Wibke (2019) KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. JCI INSIGHT, 4 (23): e131156. ISSN 2379-3708
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND. The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS. To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS. We identified a genome-wide significant (P < 5 x 10(-8)) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 x 10(-12)) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery. CONCLUSIONS. In this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; J-POINT ELEVATION; VENTRICULAR-FIBRILLATION; METAANALYSIS; MUTATION; S422L; GWAS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 09:32 |
| Last Modified: | 20 Mar 2020 09:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25688 |
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