DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was QRS duration. The EFO term heart function measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: heart function measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

N Sotoodehnia, A Isaacs, PI de Bakker, M Dörr, C Newton-Cheh, IM Nolte, P van der Harst, M Müller, M Eijgelsheim, A Alonso, AA Hicks, S Padmanabhan, C Hayward, AV Smith, O Polasek, S Giovannone, J Fu, JW Magnani, KD Marciante, A Pfeufer, SA Gharib, A Teumer, M Li, JC Bis, F Rivadeneira, T Aspelund, A Köttgen, T Johnson, K Rice, MP Sie, YA Wang, N Klopp, C Fuchsberger, SH Wild, I Mateo Leach, K Estrada, U Völker, AF Wright, FW Asselbergs, J Qu, A Chakravarti, MF Sinner, JA Kors, A Petersmann, TB Harris, EZ Soliman, PB Munroe, BM Psaty, BA Oostra, LA Cupples, S Perz, RA de Boer, AG Uitterlinden, H Völzke, TD Spector, FY Liu, E Boerwinkle, AF Dominiczak, JI Rotter, G van Herpen, D Levy, HE Wichmann, WH van Gilst, JC Witteman, HK Kroemer, WH Kao, SR Heckbert, T Meitinger, A Hofman, H Campbell, AR Folsom, DJ van Veldhuisen, C Schwienbacher, CJ O'Donnell, CB Volpato, MJ Caulfield, JM Connell, L Launer, X Lu, L Franke, RS Fehrmann, G te Meerman, HJ Groen, RK Weersma, LH van den Berg, C Wijmenga, RA Ophoff, G Navis, I Rudan, H Snieder, JF Wilson, PP Pramstaller, DS Siscovick, TJ Wang, V Gudnason, CM van Duijn, SB Felix, GI Fishman, Y Jamshidi, BH Stricker, NJ Samani, S Kääb, DE Arking

TITLE:

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

JOURNAL:

Nature genetics Dec 2010, Vol 42, pp. 1068-76

ABSTRACT:

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction. PUBMED: 21076409
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