TY - JOUR

T1 - Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits

AU - van Setten, Jessica

AU - Verweij, Niek

AU - Mbarek, Hamdi

AU - Niemeijer, Maartje N

AU - Trompet, Stella

AU - Arking, Dan E

AU - Brody, Jennifer A

AU - Gandin, Ilaria

AU - Grarup, Niels

AU - Hall, Leanne M

AU - Hemerich, Daiane

AU - Lyytikäinen, Leo-Pekka

AU - Mei, Hao

AU - Müller-Nurasyid, Martina

AU - Prins, Bram P

AU - Robino, Antonietta

AU - Smith, Albert V

AU - Warren, Helen R

AU - Asselbergs, Folkert W

AU - Boomsma, Dorret I

AU - Caulfield, Mark J

AU - Eijgelsheim, Mark

AU - Ford, Ian

AU - Hansen, Torben

AU - Harris, Tamara B

AU - Heckbert, Susan R

AU - Hottenga, Jouke-Jan

AU - Iorio, Annamaria

AU - Kors, Jan A

AU - Linneberg, Allan

AU - MacFarlane, Peter W

AU - Meitinger, Thomas

AU - Nelson, Christopher P

AU - Raitakari, Olli T

AU - Silva Aldana, Claudia T

AU - Sinagra, Gianfranco

AU - Sinner, Moritz

AU - Soliman, Elsayed Z

AU - Stoll, Monika

AU - Uitterlinden, Andre

AU - van Duijn, Cornelia M

AU - Waldenberger, Melanie

AU - Alonso, Alvaro

AU - Gasparini, Paolo

AU - Gudnason, Vilmundur

AU - Jamshidi, Yalda

AU - Kääb, Stefan

AU - Kanters, Jørgen K.

AU - Lehtimäki, Terho

AU - Munroe, Patricia B

AU - Peters, Annette

AU - Samani, Nilesh J

AU - Sotoodehnia, Nona

AU - Ulivi, Sheila

AU - Wilson, James G

AU - de Geus, Eco J C

AU - Jukema, J Wouter

AU - Stricker, Bruno

AU - van der Harst, Pim

AU - de Bakker, Paul I W

AU - Isaacs, Aaron

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41431-018-0295-z

DO - 10.1038/s41431-018-0295-z

M3 - Journal article

C2 - 30679814

VL - 27

SP - 952

EP - 962

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -