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 | |||||||||
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| 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 | |||||||||
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| Publisher License: | Creative Commons: Attribution 4.0 | |||||||||
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| PubMed ID: | 30679814 | |||||||||
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| URI: | https://openaccess.sgul.ac.uk/id/eprint/110303 | |||||||||
| Publisher's version: | https://doi.org/10.1038/s41431-018-0295-z |
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