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; +30 more... 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 NM; Hingorani, Aroon D; Samani, Nilesh J; (2011) Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy. Circulation Cardiovascular genetics, 4 (6). pp. 626-635. ISSN 1942-325X DOI: https://doi.org/10.1161/CIRCGENETICS.111.960203
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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.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
Research Centre | Centre for Global Non-Communicable Diseases (NCDs) |
PubMed ID | 21965548 |
ISI | 298414800009 |
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