Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval

Claudia Tamar Silva, Jan A. Kors, Najaf Amin, Abbas Dehghan, Jacqueline C M Witteman, Rob Willemsen, Ben A. Oostra, Cornelia M. van Duijn, Aaron Isaacs

Resultado de la investigación: Contribución a RevistaArtículo

7 Citas (Scopus)

Resumen

© 2015, The Author(s).Electrocardiogram (ECG) measurements are a powerful tool for evaluating cardiac function and are widely used for the diagnosis and prediction of a variety of conditions, including myocardial infarction, cardiac arrhythmias, and sudden cardiac death. Recently, genome-wide association studies (GWASs) identified a large number of genes related to ECG parameter variability, specifically for the QT, QRS, and PR intervals. The aims of this study were to establish the heritability of ECG traits, including indices of left ventricular hypertrophy, and to directly assess the proportion of those heritabilities explained by GWAS variants. These analyses were conducted in a large, Dutch family-based cohort study, the Erasmus Rucphen Family study using variance component methods implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) software package. Heritability estimates ranged from 34 % for QRS and Cornell voltage product to 49 % for 12-lead sum. Trait-specific GWAS findings for each trait explained a fraction of their heritability (17 % for QRS, 4 % for QT, 2 % for PR, 3 % for Sokolow–Lyon index, and 4 % for 12-lead sum). The inclusion of all ECG-associated single nucleotide polymorphisms explained an additional 6 % of the heritability of PR. In conclusion, this study shows that, although GWAS explain a portion of ECG trait variability, a large amount of heritability remains to be explained. In addition, larger GWAS for PR are likely to detect loci already identified, particularly those observed for QRS and 12-lead sum.
Idioma originalEnglish (US)
Páginas (desde-hasta)1211-1219
Número de páginas9
PublicaciónHuman Genetics
DOI
EstadoPublished - sep 18 2015

Huella dactilar

Genome-Wide Association Study
Electrocardiography
Phenotype
Sudden Cardiac Death
Left Ventricular Hypertrophy
Single Nucleotide Polymorphism
Cardiac Arrhythmias
Cohort Studies
Software
Myocardial Infarction
Genes
Lead

Citar esto

Silva, Claudia Tamar ; Kors, Jan A. ; Amin, Najaf ; Dehghan, Abbas ; Witteman, Jacqueline C M ; Willemsen, Rob ; Oostra, Ben A. ; van Duijn, Cornelia M. ; Isaacs, Aaron. / Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval. En: Human Genetics. 2015 ; pp. 1211-1219.
@article{9363b642ba9e43bab5d23abd69280e35,
title = "Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval",
abstract = "{\circledC} 2015, The Author(s).Electrocardiogram (ECG) measurements are a powerful tool for evaluating cardiac function and are widely used for the diagnosis and prediction of a variety of conditions, including myocardial infarction, cardiac arrhythmias, and sudden cardiac death. Recently, genome-wide association studies (GWASs) identified a large number of genes related to ECG parameter variability, specifically for the QT, QRS, and PR intervals. The aims of this study were to establish the heritability of ECG traits, including indices of left ventricular hypertrophy, and to directly assess the proportion of those heritabilities explained by GWAS variants. These analyses were conducted in a large, Dutch family-based cohort study, the Erasmus Rucphen Family study using variance component methods implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) software package. Heritability estimates ranged from 34 {\%} for QRS and Cornell voltage product to 49 {\%} for 12-lead sum. Trait-specific GWAS findings for each trait explained a fraction of their heritability (17 {\%} for QRS, 4 {\%} for QT, 2 {\%} for PR, 3 {\%} for Sokolow–Lyon index, and 4 {\%} for 12-lead sum). The inclusion of all ECG-associated single nucleotide polymorphisms explained an additional 6 {\%} of the heritability of PR. In conclusion, this study shows that, although GWAS explain a portion of ECG trait variability, a large amount of heritability remains to be explained. In addition, larger GWAS for PR are likely to detect loci already identified, particularly those observed for QRS and 12-lead sum.",
author = "Silva, {Claudia Tamar} and Kors, {Jan A.} and Najaf Amin and Abbas Dehghan and Witteman, {Jacqueline C M} and Rob Willemsen and Oostra, {Ben A.} and {van Duijn}, {Cornelia M.} and Aaron Isaacs",
year = "2015",
month = "9",
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doi = "10.1007/s00439-015-1595-9",
language = "English (US)",
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Silva, CT, Kors, JA, Amin, N, Dehghan, A, Witteman, JCM, Willemsen, R, Oostra, BA, van Duijn, CM & Isaacs, A 2015, 'Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval', Human Genetics, pp. 1211-1219. https://doi.org/10.1007/s00439-015-1595-9

Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval. / Silva, Claudia Tamar; Kors, Jan A.; Amin, Najaf; Dehghan, Abbas; Witteman, Jacqueline C M; Willemsen, Rob; Oostra, Ben A.; van Duijn, Cornelia M.; Isaacs, Aaron.

En: Human Genetics, 18.09.2015, p. 1211-1219.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval

AU - Silva, Claudia Tamar

AU - Kors, Jan A.

AU - Amin, Najaf

AU - Dehghan, Abbas

AU - Witteman, Jacqueline C M

AU - Willemsen, Rob

AU - Oostra, Ben A.

AU - van Duijn, Cornelia M.

AU - Isaacs, Aaron

PY - 2015/9/18

Y1 - 2015/9/18

N2 - © 2015, The Author(s).Electrocardiogram (ECG) measurements are a powerful tool for evaluating cardiac function and are widely used for the diagnosis and prediction of a variety of conditions, including myocardial infarction, cardiac arrhythmias, and sudden cardiac death. Recently, genome-wide association studies (GWASs) identified a large number of genes related to ECG parameter variability, specifically for the QT, QRS, and PR intervals. The aims of this study were to establish the heritability of ECG traits, including indices of left ventricular hypertrophy, and to directly assess the proportion of those heritabilities explained by GWAS variants. These analyses were conducted in a large, Dutch family-based cohort study, the Erasmus Rucphen Family study using variance component methods implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) software package. Heritability estimates ranged from 34 % for QRS and Cornell voltage product to 49 % for 12-lead sum. Trait-specific GWAS findings for each trait explained a fraction of their heritability (17 % for QRS, 4 % for QT, 2 % for PR, 3 % for Sokolow–Lyon index, and 4 % for 12-lead sum). The inclusion of all ECG-associated single nucleotide polymorphisms explained an additional 6 % of the heritability of PR. In conclusion, this study shows that, although GWAS explain a portion of ECG trait variability, a large amount of heritability remains to be explained. In addition, larger GWAS for PR are likely to detect loci already identified, particularly those observed for QRS and 12-lead sum.

AB - © 2015, The Author(s).Electrocardiogram (ECG) measurements are a powerful tool for evaluating cardiac function and are widely used for the diagnosis and prediction of a variety of conditions, including myocardial infarction, cardiac arrhythmias, and sudden cardiac death. Recently, genome-wide association studies (GWASs) identified a large number of genes related to ECG parameter variability, specifically for the QT, QRS, and PR intervals. The aims of this study were to establish the heritability of ECG traits, including indices of left ventricular hypertrophy, and to directly assess the proportion of those heritabilities explained by GWAS variants. These analyses were conducted in a large, Dutch family-based cohort study, the Erasmus Rucphen Family study using variance component methods implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) software package. Heritability estimates ranged from 34 % for QRS and Cornell voltage product to 49 % for 12-lead sum. Trait-specific GWAS findings for each trait explained a fraction of their heritability (17 % for QRS, 4 % for QT, 2 % for PR, 3 % for Sokolow–Lyon index, and 4 % for 12-lead sum). The inclusion of all ECG-associated single nucleotide polymorphisms explained an additional 6 % of the heritability of PR. In conclusion, this study shows that, although GWAS explain a portion of ECG trait variability, a large amount of heritability remains to be explained. In addition, larger GWAS for PR are likely to detect loci already identified, particularly those observed for QRS and 12-lead sum.

U2 - 10.1007/s00439-015-1595-9

DO - 10.1007/s00439-015-1595-9

M3 - Article

SP - 1211

EP - 1219

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

ER -