A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization

Dan Arking, Arne Pfeufer, Wendy S Post, W. H Linda Kao, Christopher Newton-Cheh, Morna Ikeda, Kristen West, Carl Kashuk, Mahmut Akyol, Siegfried Perz, Shapour Jalilzadeh, Thomas Illig, Christian Gieger, Chao Yu Guo, Martin G. Larson, H. Erich Wichmann, Eduardo Marbán, Christopher J. O'Donnell, Joel N. Hirschhorn, Stefan KääbPeter M. Spooner, Thomas Meitinger, Aravinda Chakravarti

Research output: Contribution to journalArticle

Abstract

Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation.

Original languageEnglish (US)
Pages (from-to)644-651
Number of pages8
JournalNature Genetics
Volume38
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Germany
Nitric Oxide Synthase Type I
Genome-Wide Association Study
Alleles
Genome
Mortality
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Arking, D., Pfeufer, A., Post, W. S., Kao, W. H. L., Newton-Cheh, C., Ikeda, M., ... Chakravarti, A. (2006). A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nature Genetics, 38(6), 644-651. https://doi.org/10.1038/ng1790

A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. / Arking, Dan; Pfeufer, Arne; Post, Wendy S; Kao, W. H Linda; Newton-Cheh, Christopher; Ikeda, Morna; West, Kristen; Kashuk, Carl; Akyol, Mahmut; Perz, Siegfried; Jalilzadeh, Shapour; Illig, Thomas; Gieger, Christian; Guo, Chao Yu; Larson, Martin G.; Wichmann, H. Erich; Marbán, Eduardo; O'Donnell, Christopher J.; Hirschhorn, Joel N.; Kääb, Stefan; Spooner, Peter M.; Meitinger, Thomas; Chakravarti, Aravinda.

In: Nature Genetics, Vol. 38, No. 6, 06.2006, p. 644-651.

Research output: Contribution to journalArticle

Arking, D, Pfeufer, A, Post, WS, Kao, WHL, Newton-Cheh, C, Ikeda, M, West, K, Kashuk, C, Akyol, M, Perz, S, Jalilzadeh, S, Illig, T, Gieger, C, Guo, CY, Larson, MG, Wichmann, HE, Marbán, E, O'Donnell, CJ, Hirschhorn, JN, Kääb, S, Spooner, PM, Meitinger, T & Chakravarti, A 2006, 'A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization', Nature Genetics, vol. 38, no. 6, pp. 644-651. https://doi.org/10.1038/ng1790
Arking, Dan ; Pfeufer, Arne ; Post, Wendy S ; Kao, W. H Linda ; Newton-Cheh, Christopher ; Ikeda, Morna ; West, Kristen ; Kashuk, Carl ; Akyol, Mahmut ; Perz, Siegfried ; Jalilzadeh, Shapour ; Illig, Thomas ; Gieger, Christian ; Guo, Chao Yu ; Larson, Martin G. ; Wichmann, H. Erich ; Marbán, Eduardo ; O'Donnell, Christopher J. ; Hirschhorn, Joel N. ; Kääb, Stefan ; Spooner, Peter M. ; Meitinger, Thomas ; Chakravarti, Aravinda. / A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. In: Nature Genetics. 2006 ; Vol. 38, No. 6. pp. 644-651.
@article{efcd12f71e8c4c9287886cb9f1ef02c1,
title = "A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization",
abstract = "Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60{\%} of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5{\%} of QT interval variation.",
author = "Dan Arking and Arne Pfeufer and Post, {Wendy S} and Kao, {W. H Linda} and Christopher Newton-Cheh and Morna Ikeda and Kristen West and Carl Kashuk and Mahmut Akyol and Siegfried Perz and Shapour Jalilzadeh and Thomas Illig and Christian Gieger and Guo, {Chao Yu} and Larson, {Martin G.} and Wichmann, {H. Erich} and Eduardo Marb{\'a}n and O'Donnell, {Christopher J.} and Hirschhorn, {Joel N.} and Stefan K{\"a}{\"a}b and Spooner, {Peter M.} and Thomas Meitinger and Aravinda Chakravarti",
year = "2006",
month = "6",
doi = "10.1038/ng1790",
language = "English (US)",
volume = "38",
pages = "644--651",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization

AU - Arking, Dan

AU - Pfeufer, Arne

AU - Post, Wendy S

AU - Kao, W. H Linda

AU - Newton-Cheh, Christopher

AU - Ikeda, Morna

AU - West, Kristen

AU - Kashuk, Carl

AU - Akyol, Mahmut

AU - Perz, Siegfried

AU - Jalilzadeh, Shapour

AU - Illig, Thomas

AU - Gieger, Christian

AU - Guo, Chao Yu

AU - Larson, Martin G.

AU - Wichmann, H. Erich

AU - Marbán, Eduardo

AU - O'Donnell, Christopher J.

AU - Hirschhorn, Joel N.

AU - Kääb, Stefan

AU - Spooner, Peter M.

AU - Meitinger, Thomas

AU - Chakravarti, Aravinda

PY - 2006/6

Y1 - 2006/6

N2 - Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation.

AB - Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation.

UR - http://www.scopus.com/inward/record.url?scp=33745237158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745237158&partnerID=8YFLogxK

U2 - 10.1038/ng1790

DO - 10.1038/ng1790

M3 - Article

C2 - 16648850

AN - SCOPUS:33745237158

VL - 38

SP - 644

EP - 651

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -