Sinner, Moritz F. and Porthan, Kimmo and Noseworthy, Peter A. and Havulinna, Aki S. and Tikkanen, Jani T. and Mueller-Nurasyid, Martina and Peloso, Gina and Ulivi, Sheila and Beckmann, Britt Maria and Brockhaus, A. Catharina and Cooper, Rebecca R. and Gasparini, Paolo and Hengstenberg, Christian and Hwang, Shih-Jen and Iorio, Annamaria and Junttila, M. Juhani and Klopp, Norman and Kahonen, Mika and Laaksonen, Maarit A. and Lehtimaki, Terho and Lichtner, Peter and Lyytikainen, Leo-Pekka and Martens, Eimo and Meisinger, Christa and Meitinger, Thomas and Merchant, Faisal M. and Nieminen, Markku S. and Peters, Annette and Pietila, Arto and Perz, Siegfried and Oikarinen, Lasse and Raitakari, Olli and Reinhard, Wibke and Silander, Kaisa and Thorand, Barbara and Wichmann, H. -Erich and Sinagra, Gianfranco and Viikari, Jorma and O'Donnell, Christopher J. and Ellinor, Patrick T. and Huikuri, Heikki V. and Kaeaeb, Stefan and Newton-Cheh, Christopher and Salomaa, Veikko (2012) A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern. HEART RHYTHM, 9 (10). pp. 1627-1634. ISSN 1547-5271,
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases. OBJECTIVE To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP. METHODS We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P <= 1 x 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. RESULTS Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 +/- 8.9 years, 30.3% women; ERP negative: 47.5 +/- 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P <= 1 x 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 x 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 x 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance. CONCLUSIONS In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSIENT OUTWARD CURRENT; QT INTERVAL DURATION; J-POINT ELEVATION; J-WAVE SYNDROMES; ATRIAL-FIBRILLATION; COMMON VARIANTS; VENTRICULAR-FIBRILLATION; CHANNEL; KV4.3; MUTATIONS; Early repolarization; Sudden cardiac death; Arrhythmia; GWAS; Meta-analysis; Electrocardiogram |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 May 2020 11:47 |
| Last Modified: | 05 May 2020 11:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18048 |
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