Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy

Shah, S. et al. (2011) Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy. Circulation: Cardiovascular Genetics, 4(6), pp. 626-635. (doi: 10.1161/CIRCGENETICS.111.960203)

Abstract

<p><b>Background:</b> 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.</p> <p><b>Methods and Results:</b> 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 approximate to 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=1.22X10(-7)) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74X10(-8)), 15q25.2 (NMB, rs2292462, P=3.23X10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26X10(-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.</p> <p><b>Conclusions:</b> 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.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macfarlane, Professor Peter and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna
• Authors: 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.F., Munroe, P.B., Johnson, T., Goodall, A.H., Cambien, F., Diemert, P., Hengstenberg, C., Ouwehand, W.H., Felix, J.F., Glazer, N.L., Tomaszewski, M., Burton, P.R., Tobin, M.D., van Veldhuisen, D.J., de Boer, R.A., Navis, G., van Gilst, W.H., Mayosi, B.M., Thompson, J.R., Kumari, M., Macfarlane, P.W.M., Day, I. N. M., Hingorani, A. D., and Samani, N. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation: Cardiovascular Genetics
• ISSN: 1942-325X
• ISSN (Online): 1942-3268