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Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
- Source :
- European Journal of Human Genetics, 27(6), 952-962. Nature Publishing Group, Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario, European Journal of Human Genetics, 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 & Isaacs, A 2019, ' Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits ', European Journal of Human Genetics, vol. 27, pp. 952-962 . https://doi.org/10.1038/s41431-018-0295-z, Eur. J. Hum. Genet. 27, 952-962 (2019), European Journal of Human Genetics, 27(6), 952-962. NATURE PUBLISHING GROUP, 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 & Isaacs, A 2019, ' Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits ', European Journal of Human Genetics, vol. 27, no. 6, pp. 952-962 . https://doi.org/10.1038/s41431-018-0295-z
- Publication Year :
- 2019
-
Abstract
- Publisher's version (útgefin grein)<br />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.<br />Folkert W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre.
- Subjects :
- Male
Netherlands Twin Register (NTR)
Genetics
Genetics (clinical)
PROTEIN
Genome-wide association study
Quantitative trait
Genome-wide association studies
ANNOTATION
Gene locus
Electrocardiography
Computer model
Netherlands
Priority journal
Allele
0303 health sciences
Genome
Rr interval
030305 genetics & heredity
COMMON VARIANTS
ddc
GLUCOCORTICOID-RECEPTOR
Qrs interval
Female
Cohort analysis
Erfðarannsóknir
PHOSPHOLAMBAN
Human
QT INTERVAL DURATION
Genotype
Heart rate
HEART-RATE
Exon
Single-nucleotide polymorphism
Major clinical study
Biology
Quantitative trait locus
Dutchman
Polymorphism, Single Nucleotide
QT interval
Article
Sample
03 medical and health sciences
QRS complex
Genetic
SDG 3 - Good Health and Well-being
Humans
PR interval
Gene mapping
Genetic association
MUTATIONS
Follow up
CONTRACTILITY
DNA-rannsóknir
R1
Gene frequency
POLYMORPHISM
Electrocardiogram
Single nucleotide polymorphism
Minor allele frequency
Genetic Loci
Meta analysis
Qt interval
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10184813 and 14765438
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics, 27(6), 952-962. Nature Publishing Group, Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario, European Journal of Human Genetics, 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 & Isaacs, A 2019, ' Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits ', European Journal of Human Genetics, vol. 27, pp. 952-962 . https://doi.org/10.1038/s41431-018-0295-z, Eur. J. Hum. Genet. 27, 952-962 (2019), European Journal of Human Genetics, 27(6), 952-962. NATURE PUBLISHING GROUP, 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 & Isaacs, A 2019, ' Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits ', European Journal of Human Genetics, vol. 27, no. 6, pp. 952-962 . https://doi.org/10.1038/s41431-018-0295-z
- Accession number :
- edsair.doi.dedup.....6bec5734bbaae3105adbbaea038bf1b3