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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy
Circulation: Cardiovascular Genetics, Volume 4, No. 6, Year 2011
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Description
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. © 2011 American Heart Association, Inc.
Authors & Co-Authors
Shah, Sonia H.
Unknown Affiliation
Nelson, Christopher P.
Unknown Affiliation
Gaunt, Tom R.
Unknown Affiliation
Van Der Harst, Pim
Unknown Affiliation
Barnes, Timothy A.
Unknown Affiliation
Braund, Peter S.
Unknown Affiliation
Lawlor, Debbie A.
Unknown Affiliation
Casas, Juan Pablo
Unknown Affiliation
Padmanabhan, Sandosh
Unknown Affiliation
Drenos, Fotios
Unknown Affiliation
Kivimaki, Mika Shipley
Unknown Affiliation
Talmud, Philippa J.
Unknown Affiliation
Humphries, Steve Eric
Unknown Affiliation
Whittaker, John C.
Unknown Affiliation
Morris, Richard W.
Unknown Affiliation
Whincup, Peter Hynes
Unknown Affiliation
Dominiczak, Anna F.D.
Unknown Affiliation
Munroe, Patricia B.
Unknown Affiliation
Johnson, Toby
Unknown Affiliation
Goodall, Alison H.
Unknown Affiliation
Cambien, François A.
Unknown Affiliation
Diemert, Patrick
Unknown Affiliation
Hengstenberg, Christian
Unknown Affiliation
Ouwehand, Willem Hendrik
Unknown Affiliation
Felix, Janine Frédérique
Unknown Affiliation
Glazer, Nicole L.
Unknown Affiliation
Tomaszewski, Maciej
Unknown Affiliation
Burton, Paul R.
Unknown Affiliation
Tobin, Martin D.
Unknown Affiliation
van Veldhuisen, Dirk Jan
Unknown Affiliation
De Boer, Rudolf A.
Unknown Affiliation
Navis, Gerjan
Unknown Affiliation
Van Gilst, Wiek H.
Unknown Affiliation
Mayosi, Bongani M.
Unknown Affiliation
Thompson, John R.
Unknown Affiliation
Kumari, Meena
Unknown Affiliation
Macfarlane, Peter W.
Unknown Affiliation
Day, Ian N.M.
Unknown Affiliation
Hingorani, Aroon Dinesh
Unknown Affiliation
Samani, Nilesh J.
Unknown Affiliation
Statistics
Citations: 40
Authors: 40
Affiliations: 22
Identifiers
Doi:
10.1161/CIRCGENETICS.111.960203
ISSN:
1942325X
e-ISSN:
19423268
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Approach
Quantitative