Teumer, A;
Trenkwalder, T;
Kessler, T;
Jamshidi, Y;
van den Berg, ME;
Kaess, B;
Nelson, CP;
Bastiaenen, R;
De Bortoli, M;
Rossini, A;
et al.
Teumer, A; Trenkwalder, T; Kessler, T; Jamshidi, Y; van den Berg, ME; Kaess, B; Nelson, CP; Bastiaenen, R; De Bortoli, M; Rossini, A; Deisenhofer, I; Stark, K; Assa, S; Braund, PS; Cabrera, C; Dominiczak, AF; Gögele, M; Hall, LM; Ikram, MA; Kavousi, M; Lackner, KJ; Müller, C; Münzel, T; Nauck, M; Padmanabhan, S; Pfeiffer, N; Spector, TD; Uitterlinden, AG; Verweij, N; Völker, U; Warren, HR; Zafar, M; Felix, SB; Kors, JA; Snieder, H; Munroe, PB; Pattaro, C; Fuchsberger, C; Schmidt, G; Nolte, IM; Schunkert, H; Pramstaller, P; Wild, PS; van der Harst, P; Stricker, BH; Schnabel, RB; Samani, NJ; Hengstenberg, C; Dörr, M; Behr, ER; Reinhard, W
(2019)
KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.
JCI Insight, 4 (23).
e131156.
ISSN 2379-3708
https://doi.org/10.1172/jci.insight.131156
SGUL Authors: Behr, Elijah Raphael Jamshidi, Yalda
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Abstract
BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface electrocardiogram (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<5E-8) locus in the KCND3 (potassium voltage gated channel subfamily D member 3) 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=7.7E-12), but did not reveal additional loci. Co-localization 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 a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene not only provide insights into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies. FUNDING: For detailed information per study, see Acknowledgments.
Item Type: | Article | ||||||||
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Additional Information: | © 2019, Teumer et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. | ||||||||
Keywords: | Arrhythmias, Cardiology, Genetic variation, Genetics, Ion channels, Arrhythmias, Cardiology, Genetic variation, Genetics, Ion channels | ||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) | ||||||||
Journal or Publication Title: | JCI Insight | ||||||||
ISSN: | 2379-3708 | ||||||||
Language: | eng | ||||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||||
PubMed ID: | 31600170 | ||||||||
Go to PubMed abstract | |||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/111298 | ||||||||
Publisher's version: | https://doi.org/10.1172/jci.insight.131156 |
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