Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 4, Issue 6, Pages 626-U314Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.111.960203
Keywords
electrocardiography; left ventricular hypertrophy; genetics; genetic variation; association study
Funding
- MRC [G0902037, G0600705, G0902313] Funding Source: UKRI
- British Heart Foundation [RG/08/013/25942, RG/07/008/23674, RG/08/008/25291] Funding Source: researchfish
- Medical Research Council [G8802774, G0100222, G0600705, G19/35, G0902313, G0902037] Funding Source: researchfish
- AHRQ HHS [HS06516] Funding Source: Medline
- British Heart Foundation [RG/07/008/23674, PG/07/133/24260, RG/08/013/25942, RG/08/008/25291, PG/07/131/24254] Funding Source: Medline
- Medical Research Council [G0600705, G19/35, G0100222, G8802774, G0902313, G0902037] Funding Source: Medline
- NHLBI NIH HHS [R01 HL036310, R01 HL105756, HL36310] Funding Source: Medline
- NIA NIH HHS [R01 AG013196, AG13196] Funding Source: Medline
- Department of Health Funding Source: Medline
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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 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. 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. (Circ Cardiovasc Genet. 2011;4:626-635.)
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