Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

Shah, Sonia, Nelson, Christopher P., Gaunt, Tom R., van der Harst, Pim, Barnes, Timothy, Braund, Peter S., Lawlor, Debbie A., Casas, Juan-Pablo, Padmanabhan, Sandosh, Drenos, Fotios, Kivimaki, Mika, Talmud, Philippa J., Humphries, Steve E., Whittaker, John, Morris, Richard W., Whincup, Peter H., Dominiczak, Anna, Munroe, Patricia B., Johnson, Toby, Goodall, Alison H., Cambien, Francois, Diemert, Patrick, Hengstenberg, Christian, Ouwehand, Willem H., Felix, Janine F., Glazer, Nicole L., Tomaszewski, Maciej, Burton, Paul R., Tobin, Martin D., van Veldhuisen, Dirk J., de Boer, Rudolf A., Navis, Gerjan, van Gilst, Wiek H., Mayosi, Bongani M., Thompson, John R., Kumari, Meena, MacFarlane, Peter W., Day, Ian N. M., Hingorani, Aroon D. and Samani, Nilesh J. (2011) Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy. Circulation: Cardiovascular Genetics, 4 6: 626-635. doi:10.1161/CIRCGENETICS.111.960203

Author Shah, Sonia
Nelson, Christopher P.
Gaunt, Tom R.
van der Harst, Pim
Barnes, Timothy
Braund, Peter S.
Lawlor, Debbie A.
Casas, Juan-Pablo
Padmanabhan, Sandosh
Drenos, Fotios
Kivimaki, Mika
Talmud, Philippa J.
Humphries, Steve E.
Whittaker, John
Morris, Richard W.
Whincup, Peter H.
Dominiczak, Anna
Munroe, Patricia B.
Johnson, Toby
Goodall, Alison H.
Cambien, Francois
Diemert, Patrick
Hengstenberg, Christian
Ouwehand, Willem H.
Felix, Janine F.
Glazer, Nicole L.
Tomaszewski, Maciej
Burton, Paul R.
Tobin, Martin D.
van Veldhuisen, Dirk J.
de Boer, Rudolf A.
Navis, Gerjan
van Gilst, Wiek H.
Mayosi, Bongani M.
Thompson, John R.
Kumari, Meena
MacFarlane, Peter W.
Day, Ian N. M.
Hingorani, Aroon D.
Samani, Nilesh J.
Title Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy
Journal name Circulation: Cardiovascular Genetics   Check publisher's open access policy
ISSN 1942-325X
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1161/CIRCGENETICS.111.960203
Open Access Status Not Open Access
Volume 4
Issue 6
Start page 626
End page 635
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted 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.
Keyword Association study
Genetic variation
Left ventricular hypertrophy
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HS06516
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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