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

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... Mehr ...

Verfasser: van Setten, Jessica
Verweij, Niek
Mbarek, Hamdi
Niemeijer, Maartje N.
Trompet, Stella
Arking, Dan E.
Brody, Jennifer A.
Gandin, Ilaria
Grarup, Niels
Hall, Leanne M.
Hemerich, Daiane
Lyytikäinen, Leo Pekka
Mei, Hao
Müller-Nurasyid, Martina
Prins, Bram P.
Robino, Antonietta
Smith, Albert V.
Warren, Helen R.
Asselbergs, Folkert W.
Boomsma, Dorret I.
Caulfield, Mark J.
Eijgelsheim, Mark
Ford, Ian
Hansen, Torben
Harris, Tamara B.
Heckbert, Susan R.
Hottenga, Jouke Jan
Iorio, Anita
Kors, Jan A.
Linneberg, Allan
MacFarlane, Peter W.
Meitinger, Thomas
Nelson, Christopher P.
Raitakari, Olli T.
Silva Aldana, Claudia T.
Sinagra, Gianfranco
Sinner, Moritz
Soliman, Elsayed Z.
Stoll, Monika
Uitterlinden, Andre
van Duijn, Cornelia M.
Waldenberger, Melanie
Alonso, Alvaro
Gasparini, Paolo
Gudnason, Vilmundur
Jamshidi, Yalda
Kääb, Stefan
Kanters, Jørgen K.
Lehtimäki, Terho
Munroe, Patricia B.
Peters, Annette
Samani, Nilesh J.
Sotoodehnia, Nona
Ulivi, Sheila
Wilson, James G.
de Geus, Eco J.C.
Jukema, J. Wouter
Stricker, Bruno
van der Harst, Pim
de Bakker, Paul I.W.
Isaacs, Aaron
Dokumenttyp: Artikel
Erscheinungsdatum: 2019
Reihe/Periodikum: 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
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being / name=SDG 3 - Good Health and Well-being
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-26843547
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/28706f57-bfc4-450a-b581-9338a887dea5

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.