A common variant near the KCNJ2 gene is associated with T-peak to T-end interval

Annukka Marjamaa; Lasse Oikarinen; Kimmo Porthan; Samuli Ripatti; Gina Peloso; Peter A. Noseworthy; Matti Viitasalo; Markku S. Nieminen; Lauri Toivonen; Kimmo Kontula; Leena Peltonen; Aki S. Havulinna; Antti Jula; Christopher J. O'Donnell; Christopher Newton-Cheh; Markus Perola; Veikko Salomaa

doi:10.1016/j.hrthm.2012.02.019

A common variant near the KCNJ2 gene is associated with T-peak to T-end interval

Annukka Marjamaa, Lasse Oikarinen, Kimmo Porthan, Samuli Ripatti, Gina Peloso, Peter A. Noseworthy, Matti Viitasalo, Markku S. Nieminen, Lauri Toivonen, Kimmo Kontula, Leena Peltonen, Aki S. Havulinna, Antti Jula, Christopher J. O'Donnell, Christopher Newton-Cheh, Markus Perola, Veikko Salomaa

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

BACKGROUND: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE: To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V₂, and V₅ on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10^-10). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10^-4). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10^-14). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.

Original language	English (US)
Pages (from-to)	1099-1103
Number of pages	5
Journal	Heart rhythm
Volume	9
Issue number	7
DOIs	https://doi.org/10.1016/j.hrthm.2012.02.019
State	Published - Jul 2012

Keywords

Electrocardiogram
Gene
Polymorphism
Repolarization
T wave

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1016/j.hrthm.2012.02.019

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Marjamaa, A., Oikarinen, L., Porthan, K., Ripatti, S., Peloso, G., Noseworthy, P. A., Viitasalo, M., Nieminen, M. S., Toivonen, L., Kontula, K., Peltonen, L., Havulinna, A. S., Jula, A., O'Donnell, C. J., Newton-Cheh, C., Perola, M., & Salomaa, V. (2012). A common variant near the KCNJ2 gene is associated with T-peak to T-end interval. Heart rhythm, 9(7), 1099-1103. https://doi.org/10.1016/j.hrthm.2012.02.019

Marjamaa, A, Oikarinen, L, Porthan, K, Ripatti, S, Peloso, G, Noseworthy, PA, Viitasalo, M, Nieminen, MS, Toivonen, L, Kontula, K, Peltonen, L, Havulinna, AS, Jula, A, O'Donnell, CJ, Newton-Cheh, C, Perola, M & Salomaa, V 2012, 'A common variant near the KCNJ2 gene is associated with T-peak to T-end interval', Heart rhythm, vol. 9, no. 7, pp. 1099-1103. https://doi.org/10.1016/j.hrthm.2012.02.019

@article{c6c497162ef24967aca27a5c3956cdaf,

title = "A common variant near the KCNJ2 gene is associated with T-peak to T-end interval",

abstract = "BACKGROUND: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE: To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V2, and V5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10-10). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10-4). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10-14). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.",

keywords = "Electrocardiogram, Gene, Polymorphism, Repolarization, T wave",

author = "Annukka Marjamaa and Lasse Oikarinen and Kimmo Porthan and Samuli Ripatti and Gina Peloso and Noseworthy, {Peter A.} and Matti Viitasalo and Nieminen, {Markku S.} and Lauri Toivonen and Kimmo Kontula and Leena Peltonen and Havulinna, {Aki S.} and Antti Jula and O'Donnell, {Christopher J.} and Christopher Newton-Cheh and Markus Perola and Veikko Salomaa",

note = "Funding Information: Leena Peltonen is deceased. Dr Porthan, Dr Oikarinen, and Dr Viitasalo were financially supported by the Finnish Foundation for Cardiovascular Research. Dr Porthan was also supported by the Orion-Farmos Research Foundation. Dr Perola was supported by the Finnish Academy SALVE program “Pubgensense” 129322 and the Finnish Foundation for Cardiovascular Research. Dr Salomaa was supported by the Academy of Finland (grant numbers 129494 and 139635 ). Dr Kontula was supported by grants from the Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research . The Framingham Heart Study work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine (contract number N01-HC-25195), its contract with Affymetrix, Inc, for genotyping services (contract number N02-HL-6-4278), and the Doris Duke Charitable Foundation (to Dr Newton-Cheh) and Burroughs Wellcome Fund (to Dr Newton-Cheh), based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. ",

year = "2012",

month = jul,

doi = "10.1016/j.hrthm.2012.02.019",

language = "English (US)",

volume = "9",

pages = "1099--1103",

journal = "Heart rhythm",

issn = "1547-5271",

publisher = "Elsevier",

number = "7",

}

TY - JOUR

T1 - A common variant near the KCNJ2 gene is associated with T-peak to T-end interval

AU - Marjamaa, Annukka

AU - Oikarinen, Lasse

AU - Porthan, Kimmo

AU - Ripatti, Samuli

AU - Peloso, Gina

AU - Noseworthy, Peter A.

AU - Viitasalo, Matti

AU - Nieminen, Markku S.

AU - Toivonen, Lauri

AU - Kontula, Kimmo

AU - Peltonen, Leena

AU - Havulinna, Aki S.

AU - Jula, Antti

AU - O'Donnell, Christopher J.

AU - Newton-Cheh, Christopher

AU - Perola, Markus

AU - Salomaa, Veikko

N1 - Funding Information: Leena Peltonen is deceased. Dr Porthan, Dr Oikarinen, and Dr Viitasalo were financially supported by the Finnish Foundation for Cardiovascular Research. Dr Porthan was also supported by the Orion-Farmos Research Foundation. Dr Perola was supported by the Finnish Academy SALVE program “Pubgensense” 129322 and the Finnish Foundation for Cardiovascular Research. Dr Salomaa was supported by the Academy of Finland (grant numbers 129494 and 139635 ). Dr Kontula was supported by grants from the Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research . The Framingham Heart Study work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine (contract number N01-HC-25195), its contract with Affymetrix, Inc, for genotyping services (contract number N02-HL-6-4278), and the Doris Duke Charitable Foundation (to Dr Newton-Cheh) and Burroughs Wellcome Fund (to Dr Newton-Cheh), based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project.

PY - 2012/7

Y1 - 2012/7

N2 - BACKGROUND: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE: To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V2, and V5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10-10). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10-4). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10-14). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.

AB - BACKGROUND: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE: To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V2, and V5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10-10). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10-4). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10-14). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.

KW - Electrocardiogram

KW - Gene

KW - Polymorphism

KW - Repolarization

KW - T wave

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U2 - 10.1016/j.hrthm.2012.02.019

DO - 10.1016/j.hrthm.2012.02.019

M3 - Article

C2 - 22342860

AN - SCOPUS:84862858285

SN - 1547-5271

VL - 9

SP - 1099

EP - 1103

JO - Heart rhythm

JF - Heart rhythm

IS - 7

ER -

A common variant near the KCNJ2 gene is associated with T-peak to T-end interval

Abstract

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