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.

Additional Metadata
Keywords Association study, Electrocardiography, Genetic variation, Genetics, Left ventricular hypertrophy
Persistent URL dx.doi.org/10.1161/CIRCGENETICS.111.960203, hdl.handle.net/1765/34642
Citation
Shah, S., Nelson, C.P., Gaunt, T.R., van der Harst, P., Barnes, T.A., Braund, P.S., … Samani, N.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