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Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.

van Setten, J; Verweij, N; Mbarek, H; Niemeijer, MN; Trompet, S; Arking, DE; Brody, JA; Gandin, I; Grarup, N; Hall, LM; et al. van Setten, J; Verweij, N; Mbarek, H; Niemeijer, MN; Trompet, S; Arking, DE; Brody, JA; Gandin, I; Grarup, N; Hall, LM; Hemerich, D; Lyytikäinen, L-P; Mei, H; Müller-Nurasyid, M; Prins, BP; Robino, A; Smith, AV; Warren, HR; Asselbergs, FW; Boomsma, DI; Caulfield, MJ; Eijgelsheim, M; Ford, I; Hansen, T; Harris, TB; Heckbert, SR; Hottenga, J-J; Iorio, A; Kors, JA; Linneberg, A; MacFarlane, PW; Meitinger, T; Nelson, CP; Raitakari, OT; Silva Aldana, CT; Sinagra, G; Sinner, M; Soliman, EZ; Stoll, M; Uitterlinden, A; van Duijn, CM; Waldenberger, M; Alonso, A; Gasparini, P; Gudnason, V; Jamshidi, Y; Kääb, S; Kanters, JK; Lehtimäki, T; Munroe, PB; Peters, A; Samani, NJ; Sotoodehnia, N; Ulivi, S; Wilson, JG; de Geus, EJC; Jukema, JW; Stricker, B; van der Harst, P; de Bakker, PIW; Isaacs, A (2019) Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits. Eur J Hum Genet, 27 (6). pp. 952-962. ISSN 1476-5438 https://doi.org/10.1038/s41431-018-0295-z
SGUL Authors: Jamshidi, Yalda

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Abstract

Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.

Item Type: Article
Additional Information: © The Author(s) 2019. This article is published with open access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: 0604 Genetics, Genetics & Heredity
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Eur J Hum Genet
ISSN: 1476-5438
Language: eng
Dates:
DateEvent
June 2019Published
24 January 2019Published Online
16 October 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
G9521010DMedical Research Councilhttp://dx.doi.org/10.13039/501100000265
PG/12/38/29615British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 30679814
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/110303
Publisher's version: https://doi.org/10.1038/s41431-018-0295-z

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