; 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 ; 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 N.M. ; Hingorani, Aroon D. ; Samani, Nilesh J. | Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Circulation: Cardiovascular Genetics | ||||
| Verlag: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Ort der Veröffentlichung: | PHILADELPHIA | ||||
| Band: | 4 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 6 | ||||
| Seitenbereich: | S. 626-635 | ||||
| Datum: | 2011 | ||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin II | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | GENOME-WIDE ASSOCIATION; LINKAGE ANALYSIS; COMMON VARIANTS; BLOOD-PRESSURE; CARDIOMYOPATHY; HYPERTENSION; DURATION; HEART; IDENTIFICATION; METAANALYSIS; electrocardiography; left ventricular hypertrophy; genetics; genetic variation; association study | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 64323 |
Zusammenfassung
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, ...

Zusammenfassung
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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