University of Leicester
Browse
s41431-018-0295-z.pdf (2.04 MB)

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

Download (2.04 MB)
journal contribution
posted on 2019-09-17, 15:00 authored by J van Setten, N Verweij, H Mbarek, MN Niemeijer, S Trompet, DE Arking, JA Brody, I Gandin, N Grarup, LM Hall, D Hemerich, L-P Lyytikäinen, H Mei, M Müller-Nurasyid, BP Prins, A Robino, AV Smith, HR Warren, FW Asselbergs, DI Boomsma, MJ Caulfield, M Eijgelsheim, I Ford, T Hansen, TB Harris, SR Heckbert, J-J Hottenga, A Iorio, JA Kors, A Linneberg, PW MacFarlane, T Meitinger, CP Nelson, OT Raitakari, CT Silva Aldana, G Sinagra, M Sinner, EZ Soliman, M Stoll, A Uitterlinden, CM van Duijn, M Waldenberger, A Alonso, P Gasparini, V Gudnason, Y Jamshidi, S Kääb, JK Kanters, T Lehtimäki, PB Munroe, A Peters, NJ Samani, N Sotoodehnia, S Ulivi, JG Wilson, EJC de Geus, JW Jukema, B Stricker, P van der Harst, PIW de Bakker, A Isaacs
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.

Funding

Folkert W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre.

History

Citation

European Journal of Human Genetics, 2019, 27, pp. 952–962

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

European Journal of Human Genetics

Publisher

Springer Nature for European Society of Human Genetics

eissn

1476-5438

Acceptance date

2018-10-16

Copyright date

2019

Available date

2019-09-17

Publisher version

https://www.nature.com/articles/s41431-018-0295-z

Notes

The online version of this article (https://doi.org/10.1038/s41431-018-0295-z) contains supplementary material, which is available to authorized users.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC