Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy
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.
|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|
|Journal||Circulation: Cardiovascular Genetics|
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