Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy
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Published:2011-12
Issue:6
Volume:4
Page:626-635
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ISSN:1942-325X
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Container-title:Circulation: Cardiovascular Genetics
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language:en
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Short-container-title:Circ Cardiovasc Genet
Author:
Shah Sonia1, Nelson Christopher P.1, Gaunt Tom R.1, van der Harst Pim1, Barnes Timothy1, Braund Peter S.1, Lawlor Debbie A.1, Casas Juan-Pablo1, Padmanabhan Sandosh1, Drenos Fotios1, Kivimaki Mika1, Talmud Philippa J.1, Humphries Steve E.1, Whittaker John1, Morris Richard W.1, Whincup Peter H.1, Dominiczak Anna1, Munroe Patricia B.1, Johnson Toby1, Goodall Alison H.1, Cambien Francois1, Diemert Patrick1, Hengstenberg Christian1, Ouwehand Willem H.1, Felix Janine F.1, Glazer Nicole L.1, Tomaszewski Maciej1, Burton Paul R.1, Tobin Martin D.1, van Veldhuisen Dirk J.1, de Boer Rudolf A.1, Navis Gerjan1, van Gilst Wiek H.1, Mayosi Bongani M.1, Thompson John R.1, Kumari Meena1, MacFarlane Peter W.1, Day Ian N.M.1, Hingorani Aroon D.1, Samani Nilesh J.1
Affiliation:
1. From the Department of Genetics, Evolution and Environment (S.S., S.E.H.), University College London, London, United Kingdom; Department of Cardiovascular Sciences C.P.N., T.B., P.S.B., A.H.G., M.T., N.J.S.), University of Leicester, Leicester, United Kingdom; Leicester Cardiovascular Biomedical Research Unit (C.P.N., A.H.G., M.T., P.R.B., N.J.S.), Glenfield Hospital, Leicester, United Kingdom; MRC Centre for Causal Analyses in Translational Epidemiology (T.R.G., D.A.L., I.N.M.D.), School of Social...
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics (clinical),Cardiology and Cardiovascular Medicine,Genetics
Cited by
26 articles.
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