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

van Setten, J. et al. (2019) Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits. European Journal of Human Genetics, (doi:10.1038/s41431-018-0295-z) (PMID:30679814) (Early Online Publication)

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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:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Ford, Professor Ian
Authors: van Setten, J., Verweij, N., Mbarek, H., Niemeijer, M. N., Trompet, S., Arking, D. E., Brody, J. A., Gandin, I., Grarup, N., Hall, L. M., Hemerich, D., Lyytikäinen, L.-P., Mei, H., Müller-Nurasyid, M., Prins, B. P., Robino, A., Smith, A. V., Warren, H. R., Asselbergs, F. W., Boomsma, D. I., Caulfield, M. J., Eijgelsheim, M., Ford, I., Hansen, T., Harris, T. B., Heckbert, S. R., Hottenga, J.-J., Iorio, A., Kors, J. A., Linneberg, A., MacFarlane, P. W., Meitinger, T., Nelson, C. P., Raitakari, O. T., Silva Aldana, C. T., Sinagra, G., Sinner, M., Soliman, E. Z., Stoll, M., Uitterlinden, A., van Duijn, C. M., Waldenberger, M., Alonso, A., Gasparini, P., Gudnason, V., Jamshidi, Y., Kääb, S., Kanters, J. K., Lehtimäki, T., Munroe, P. B., Peters, A., Samani, N. J., Sotoodehnia, N., Ulivi, S., Wilson, J. G., de Geus, E. J. C., Jukema, J. W., Stricker, B., van der Harst, P., de Bakker, P. I. W., and Isaacs, A.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Human Genetics
Publisher:Springer Nature
ISSN:1018-4813
ISSN (Online):1476-5438
Published Online:24 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in European Journal of Human Genetics 2019
Publisher Policy:Reproduced under a Creative Commons License

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