Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

Sonia Shah; Christopher P Nelson; Tom R Gaunt; Pim van der Harst; Timothy Barnes; Peter S Braund; Debbie A Lawlor; Juan-Pablo Casas; Sandosh Padmanabhan; Fotios Drenos; Mika Kivimaki; Philippa J Talmud; Steve E Humphries; John Whittaker; Richard W Morris; Peter H Whincup; Anna Dominiczak; Patricia B Munroe; Toby Johnson; Alison H Goodall; Francois Cambien; Patrick Diemert; Christian Hengstenberg; Willem H Ouwehand; Janine F Felix; Nicole L Glazer; Maciej Tomaszewski; Paul R Burton; Martin D Tobin; Dirk J van Veldhuisen; Rudolf A de Boer; Gerjan Navis; Wiek H van Gilst; Bongani M Mayosi; John R Thompson; Meena Kumari; Peter W MacFarlane; Ian N M Day; Aroon D Hingorani; Nilesh J Samani

doi:10.1161/CIRCGENETICS.111.960203

Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

Sonia Shah, Christopher P Nelson, Tom R Gaunt, Pim van der Harst, Timothy Barnes, Peter S Braund, Debbie A Lawlor, Juan-Pablo Casas, Sandosh Padmanabhan, Fotios Drenos, Mika Kivimaki, Philippa J Talmud, Steve E Humphries, John Whittaker, Richard W Morris, Peter H Whincup, Anna Dominiczak, Patricia B Munroe, Toby Johnson, Alison H GoodallFrancois Cambien, Patrick Diemert, Christian Hengstenberg, Willem H Ouwehand, Janine F Felix, Nicole L Glazer, Maciej Tomaszewski, Paul R Burton, Martin D Tobin, Dirk J van Veldhuisen, Rudolf A de Boer, Gerjan Navis, Wiek H van Gilst, Bongani M Mayosi, John R Thompson, Meena Kumari, Peter W MacFarlane, Ian N M Day, Aroon D Hingorani, Nilesh J Samani

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

Abstract

BACKGROUND: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH.

METHODS AND RESULTS: We calculated the Sokolow-Lyon index, Cornell product, 12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals from 3 population-based cohorts and typed their DNA using a customized gene array (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in ≈2100 genes of cardiovascular relevance. We followed-up promising associations in 11 777 additional individuals. We identified and replicated 4 loci associated with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22 × 10(-7)) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74 × 10(-8)), 15q25.2 (NMB, rs2292462, P=3.23 × 10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26 × 10(-7)) with the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12-lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI: 1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2 loci showed significant expression quantitative trait loci effects in monocytes.

CONCLUSIONS: These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.

Original language	English
Pages (from-to)	626-35
Number of pages	10
Journal	Circulation. Cardiovascular Genetics
Volume	4
Issue number	6
DOIs	https://doi.org/10.1161/CIRCGENETICS.111.960203
Publication status	Published - Dec 2011
Externally published	Yes

Keywords

Adult
Aged
Cohort Studies
Electrocardiography
Female
Genetic Loci
Humans
Hypertrophy, Left Ventricular/diagnosis
Male
Middle Aged
Prognosis

Access to Document

10.1161/CIRCGENETICS.111.960203

Cite this

Shah, S., Nelson, C. P., Gaunt, T. R., van der Harst, P., Barnes, T., Braund, P. S., Lawlor, D. A., Casas, J.-P., Padmanabhan, S., Drenos, F., Kivimaki, M., Talmud, P. J., Humphries, S. E., Whittaker, J., Morris, R. W., Whincup, P. H., Dominiczak, A., Munroe, P. B., Johnson, T., ... Samani, N. J. (2011). Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy. Circulation. Cardiovascular Genetics, 4(6), 626-35. https://doi.org/10.1161/CIRCGENETICS.111.960203

@article{12bb49ac5b2143eca5f7d095da2184a1,

title = "Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy",

abstract = "BACKGROUND: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH.METHODS AND RESULTS: We calculated the Sokolow-Lyon index, Cornell product, 12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals from 3 population-based cohorts and typed their DNA using a customized gene array (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in ≈2100 genes of cardiovascular relevance. We followed-up promising associations in 11 777 additional individuals. We identified and replicated 4 loci associated with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22 × 10(-7)) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74 × 10(-8)), 15q25.2 (NMB, rs2292462, P=3.23 × 10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26 × 10(-7)) with the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12-lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI: 1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2 loci showed significant expression quantitative trait loci effects in monocytes.CONCLUSIONS: These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.",

keywords = "Adult, Aged, Cohort Studies, Electrocardiography, Female, Genetic Loci, Humans, Hypertrophy, Left Ventricular/diagnosis, Male, Middle Aged, Prognosis",

author = "Sonia Shah and Nelson, {Christopher P} and Gaunt, {Tom R} and {van der Harst}, Pim and Timothy Barnes and Braund, {Peter S} and Lawlor, {Debbie A} and Juan-Pablo Casas and Sandosh Padmanabhan and Fotios Drenos and Mika Kivimaki and Talmud, {Philippa J} and Humphries, {Steve E} and John Whittaker and Morris, {Richard W} and Whincup, {Peter H} and Anna Dominiczak and Munroe, {Patricia B} and Toby Johnson and Goodall, {Alison H} and Francois Cambien and Patrick Diemert and Christian Hengstenberg and Ouwehand, {Willem H} and Felix, {Janine F} and Glazer, {Nicole L} and Maciej Tomaszewski and Burton, {Paul R} and Tobin, {Martin D} and {van Veldhuisen}, {Dirk J} and {de Boer}, {Rudolf A} and Gerjan Navis and {van Gilst}, {Wiek H} and Mayosi, {Bongani M} and Thompson, {John R} and Meena Kumari and MacFarlane, {Peter W} and Day, {Ian N M} and Hingorani, {Aroon D} and Samani, {Nilesh J}",

year = "2011",

month = dec,

doi = "10.1161/CIRCGENETICS.111.960203",

language = "English",

volume = "4",

pages = "626--35",

number = "6",

}

Shah, S, Nelson, CP, Gaunt, TR, van der Harst, P, Barnes, T, Braund, PS, Lawlor, DA, Casas, J-P, Padmanabhan, S, Drenos, F, Kivimaki, M, Talmud, PJ, Humphries, SE, Whittaker, J, Morris, RW, Whincup, PH, Dominiczak, A, Munroe, PB, Johnson, T, Goodall, AH, Cambien, F, Diemert, P, Hengstenberg, C, Ouwehand, WH, Felix, JF, Glazer, NL, Tomaszewski, M, Burton, PR, Tobin, MD, van Veldhuisen, DJ, de Boer, RA, Navis, G, van Gilst, WH, Mayosi, BM, Thompson, JR, Kumari, M, MacFarlane, PW, Day, INM, Hingorani, AD & Samani, NJ 2011, 'Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy', Circulation. Cardiovascular Genetics, vol. 4, no. 6, pp. 626-35. https://doi.org/10.1161/CIRCGENETICS.111.960203

TY - JOUR

T1 - Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

AU - Shah, Sonia

AU - Nelson, Christopher P

AU - Gaunt, Tom R

AU - van der Harst, Pim

AU - Barnes, Timothy

AU - Braund, Peter S

AU - Lawlor, Debbie A

AU - Casas, Juan-Pablo

AU - Padmanabhan, Sandosh

AU - Drenos, Fotios

AU - Kivimaki, Mika

AU - Talmud, Philippa J

AU - Humphries, Steve E

AU - Whittaker, John

AU - Morris, Richard W

AU - Whincup, Peter H

AU - Dominiczak, Anna

AU - Munroe, Patricia B

AU - Johnson, Toby

AU - Goodall, Alison H

AU - Cambien, Francois

AU - Diemert, Patrick

AU - Hengstenberg, Christian

AU - Ouwehand, Willem H

AU - Felix, Janine F

AU - Glazer, Nicole L

AU - Tomaszewski, Maciej

AU - Burton, Paul R

AU - Tobin, Martin D

AU - van Veldhuisen, Dirk J

AU - de Boer, Rudolf A

AU - Navis, Gerjan

AU - van Gilst, Wiek H

AU - Mayosi, Bongani M

AU - Thompson, John R

AU - Kumari, Meena

AU - MacFarlane, Peter W

AU - Day, Ian N M

AU - Hingorani, Aroon D

AU - Samani, Nilesh J

PY - 2011/12

Y1 - 2011/12

N2 - BACKGROUND: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH.METHODS AND RESULTS: We calculated the Sokolow-Lyon index, Cornell product, 12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals from 3 population-based cohorts and typed their DNA using a customized gene array (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in ≈2100 genes of cardiovascular relevance. We followed-up promising associations in 11 777 additional individuals. We identified and replicated 4 loci associated with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22 × 10(-7)) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74 × 10(-8)), 15q25.2 (NMB, rs2292462, P=3.23 × 10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26 × 10(-7)) with the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12-lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI: 1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2 loci showed significant expression quantitative trait loci effects in monocytes.CONCLUSIONS: These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.

AB - BACKGROUND: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH.METHODS AND RESULTS: We calculated the Sokolow-Lyon index, Cornell product, 12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals from 3 population-based cohorts and typed their DNA using a customized gene array (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in ≈2100 genes of cardiovascular relevance. We followed-up promising associations in 11 777 additional individuals. We identified and replicated 4 loci associated with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22 × 10(-7)) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74 × 10(-8)), 15q25.2 (NMB, rs2292462, P=3.23 × 10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26 × 10(-7)) with the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12-lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI: 1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2 loci showed significant expression quantitative trait loci effects in monocytes.CONCLUSIONS: These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.

KW - Adult

KW - Aged

KW - Cohort Studies

KW - Electrocardiography

KW - Female

KW - Genetic Loci

KW - Humans

KW - Hypertrophy, Left Ventricular/diagnosis

KW - Male

KW - Middle Aged

KW - Prognosis

U2 - 10.1161/CIRCGENETICS.111.960203

DO - 10.1161/CIRCGENETICS.111.960203

M3 - Article

C2 - 21965548

SN - 1942-3268

VL - 4

SP - 626

EP - 635

JO - Circulation. Cardiovascular Genetics

JF - Circulation. Cardiovascular Genetics

IS - 6

ER -

Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

Abstract

Keywords

Access to Document

Fingerprint

Cite this