ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
Nathan A. Bihlmeyer; Jennifer A. Brody; Albert Vernon Smith; Helen R. Warren; Honghuang Lin; Aaron Isaacs; Ching-Ti Liu; Jonathan Marten; Farid Radmanesh; Leanne M. Hall; Niels Grarup; Hao Mei; Martina Müller-Nurasyid; Jennifer E. Huffman; Niek Verweij; Xiuqing Guo; Jie Yao; Ruifang Li-Gao; Marten van den Berg; Stefan Weiss; Bram P. Prins; Jessica van Setten; Jeffrey Haessler; Leo-Pekka Lyytikäinen; Man Li; Alvaro Alonso; Elsayed Z. Soliman; Joshua C. Bis; Tom Austin; Yii-Der Ida Chen; Bruce M. Psaty; Tamara B. Harrris; Lenore J. Launer; Sandosh Padmanabhan; Anna Dominiczak; Paul L. Huang; Zhijun Xie; Patrick T. Ellinor; Jan A. Kors; Archie Campbell; Alison D. Murray; Christopher P. Nelson; Martin D. Tobin; Jette Bork-Jensen; Torben Hansen; Oluf Pedersen; Allan Linneberg; Moritz F. Sinner; Annette Peters; Melanie Waldenberger; Thomas Meitinger; Siegfried Perz; Ivana Kolcic; Igor Rudan; Rudolf A. de Boer; Peter van der Meer; Henry J. Lin; Kent D. Taylor; Renée de Mutsert; Stella Trompet; J. Wouter Jukema; Arie C. Maan; Bruno H.C. Stricker; Fernando Rivadeneira; André Uitterlinden; Uwe Völker; Georg Homuth; Henry Völzke; Stephan B. Felix; Massimo Mangino; Timothy D. Spector; Michiel L. Bots; Marco Perez; Olli T. Raitakari; Mika Kähönen; Nina Mononen; Vilmundur Gudnason; Patricia B. Munroe; Steven A. Lubitz; Cornelia M. van Duijn; Christopher H. Newton-Cheh; Caroline Hayward; Jonathan Rosand; Nilesh J. Samani; Jørgen K. Kanters; James G. Wilson; Stefan Kääb; Ozren Polasek; Pim van der Harst; Susan R. Heckbert; Jerome I. Rotter; Dennis O. Mook-Kanamori; Mark Eijgelsheim; Marcus Dörr; Yalda Jamshidi; Folkert W. Asselbergs; Charles Kooperberg; Terho Lehtimäki; Dan E. Arking; Nona Sotoodehnia
ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals
Nathan A. Bihlmeyer
Jennifer A. Brody
Albert Vernon Smith
Helen R. Warren
Honghuang Lin
Aaron Isaacs
Ching-Ti Liu
Jonathan Marten
Farid Radmanesh
Leanne M. Hall
Niels Grarup
Hao Mei
Martina Müller-Nurasyid
Jennifer E. Huffman
Niek Verweij
Xiuqing Guo
Jie Yao
Ruifang Li-Gao
Marten van den Berg
Stefan Weiss
Bram P. Prins
Jessica van Setten
Jeffrey Haessler
Leo-Pekka Lyytikäinen
Man Li
Alvaro Alonso
Elsayed Z. Soliman
Joshua C. Bis
Tom Austin
Yii-Der Ida Chen
Bruce M. Psaty
Tamara B. Harrris
Lenore J. Launer
Sandosh Padmanabhan
Anna Dominiczak
Paul L. Huang
Zhijun Xie
Patrick T. Ellinor
Jan A. Kors
Archie Campbell
Alison D. Murray
Christopher P. Nelson
Martin D. Tobin
Jette Bork-Jensen
Torben Hansen
Oluf Pedersen
Allan Linneberg
Moritz F. Sinner
Annette Peters
Melanie Waldenberger
Thomas Meitinger
Siegfried Perz
Ivana Kolcic
Igor Rudan
Rudolf A. de Boer
Peter van der Meer
Henry J. Lin
Kent D. Taylor
Renée de Mutsert
Stella Trompet
J. Wouter Jukema
Arie C. Maan
Bruno H.C. Stricker
Fernando Rivadeneira
André Uitterlinden
Uwe Völker
Georg Homuth
Henry Völzke
Stephan B. Felix
Massimo Mangino
Timothy D. Spector
Michiel L. Bots
Marco Perez
Olli T. Raitakari
Mika Kähönen
Nina Mononen
Vilmundur Gudnason
Patricia B. Munroe
Steven A. Lubitz
Cornelia M. van Duijn
Christopher H. Newton-Cheh
Caroline Hayward
Jonathan Rosand
Nilesh J. Samani
Jørgen K. Kanters
James G. Wilson
Stefan Kääb
Ozren Polasek
Pim van der Harst
Susan R. Heckbert
Jerome I. Rotter
Dennis O. Mook-Kanamori
Mark Eijgelsheim
Marcus Dörr
Yalda Jamshidi
Folkert W. Asselbergs
Charles Kooperberg
Terho Lehtimäki
Dan E. Arking
Nona Sotoodehnia
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 [27094]