ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
Jennifer E. Huffman; Aaron Isaacs; Niels Grarup; Leo-Pekka Lyytikäinen; Niek Verweij; Alison D. Murray; Stephan B. Felix; Nona Sotoodehnia; Folkert W. Asselbergs; Jonathan Rosand; Caroline Hayward; Henry J. Lin; Ching-Ti Liu; Nathan A. Bihlmeyer; Michiel L. Bots; Zhijun Xie; Jie Yao; Ivana Kolcic; Fernando Rivadeneira; Christopher P. Nelson; Arie C. Maan; Stella Trompet; Anna Dominiczak; Cornelia M. van Duijn; Patricia B. Munroe; Martin D. Tobin; Sandosh Padmanabhan; Hao Mei; Bruno H.C. Stricker; Stefan Kääb; Stefan Weiss; Marco Perez; Jeffrey Haessler; Archie Campbell; Georg Homuth; Charles Kooperberg; Alvaro Alonso; Dennis O. Mook-Kanamori; Nina Mononen; Christopher H. Newton-Cheh; Martina Müller-Nurasyid; Ruifang Li-Gao; J. Wouter Jukema; Kent D. Taylor; Yalda Jamshidi; Elsayed Z. Soliman; Marcus Dörr; Bruce M. Psaty; Terho Lehtimäki; Ozren Polasek; James G. Wilson; Igor Rudan; Honghuang Lin; Jørgen K. Kanters; Tom Austin; Rudolf A. de Boer; Jonathan Marten; Jennifer A. Brody; André Uitterlinden; Moritz F. Sinner; Massimo Mangino; Pim van der Harst; Torben Hansen; Siegfried Perz; Paul L. Huang; Marten van den Berg; Joshua C. Bis; Yii-Der Ida Chen; Nilesh J. Samani; Uwe Völker; Dan E. Arking; Helen R. Warren; Leanne M. Hall; Olli T. Raitakari; Lenore J. Launer; Farid Radmanesh; Vilmundur Gudnason; Peter van der Meer; Patrick T. Ellinor; Renée de Mutsert; Xiuqing Guo; Thomas Meitinger; Oluf Pedersen; Henry Völzke; Timothy D. Spector; Melanie Waldenberger; Bram P. Prins; Susan R. Heckbert; Jan A. Kors; Annette Peters; Jessica van Setten; Mika Kähönen; Tamara B. Harrris; Jerome I. Rotter; Allan Linneberg; Albert Vernon Smith; Steven A. Lubitz; Man Li; Mark Eijgelsheim; Jette Bork-Jensen
ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
Jennifer E. Huffman
Aaron Isaacs
Niels Grarup
Leo-Pekka Lyytikäinen
Niek Verweij
Alison D. Murray
Stephan B. Felix
Nona Sotoodehnia
Folkert W. Asselbergs
Jonathan Rosand
Caroline Hayward
Henry J. Lin
Ching-Ti Liu
Nathan A. Bihlmeyer
Michiel L. Bots
Zhijun Xie
Jie Yao
Ivana Kolcic
Fernando Rivadeneira
Christopher P. Nelson
Arie C. Maan
Stella Trompet
Anna Dominiczak
Cornelia M. van Duijn
Patricia B. Munroe
Martin D. Tobin
Sandosh Padmanabhan
Hao Mei
Bruno H.C. Stricker
Stefan Kääb
Stefan Weiss
Marco Perez
Jeffrey Haessler
Archie Campbell
Georg Homuth
Charles Kooperberg
Alvaro Alonso
Dennis O. Mook-Kanamori
Nina Mononen
Christopher H. Newton-Cheh
Martina Müller-Nurasyid
Ruifang Li-Gao
J. Wouter Jukema
Kent D. Taylor
Yalda Jamshidi
Elsayed Z. Soliman
Marcus Dörr
Bruce M. Psaty
Terho Lehtimäki
Ozren Polasek
James G. Wilson
Igor Rudan
Honghuang Lin
Jørgen K. Kanters
Tom Austin
Rudolf A. de Boer
Jonathan Marten
Jennifer A. Brody
André Uitterlinden
Moritz F. Sinner
Massimo Mangino
Pim van der Harst
Torben Hansen
Siegfried Perz
Paul L. Huang
Marten van den Berg
Joshua C. Bis
Yii-Der Ida Chen
Nilesh J. Samani
Uwe Völker
Dan E. Arking
Helen R. Warren
Leanne M. Hall
Olli T. Raitakari
Lenore J. Launer
Farid Radmanesh
Vilmundur Gudnason
Peter van der Meer
Patrick T. Ellinor
Renée de Mutsert
Xiuqing Guo
Thomas Meitinger
Oluf Pedersen
Henry Völzke
Timothy D. Spector
Melanie Waldenberger
Bram P. Prins
Susan R. Heckbert
Jan A. Kors
Annette Peters
Jessica van Setten
Mika Kähönen
Tamara B. Harrris
Jerome I. Rotter
Allan Linneberg
Albert Vernon Smith
Steven A. Lubitz
Man Li
Mark Eijgelsheim
Jette Bork-Jensen
LIPPINCOTT WILLIAMS & WILKINS
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042719113
https://urn.fi/URN:NBN:fi-fe2021042719113
Tiivistelmä
BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.
Kokoelmat
- Rinnakkaistallenteet [19207]