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

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

doi:10.1038/ng.716

Benutzer: Gast

journal article

Dokumenttyp:: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
Autor(en):: Sotoodehnia, N; Isaacs, A; de Bakker, PI; Dörr, M; Newton-Cheh, C; Nolte, IM; van der Harst, P; Muller, M; Eijgelsheim, M; Alonso, A; Hicks, AA; Padmanabhan, S; Hayward, C; Smith, AV; Polasek, O; Giovannone, S; Fu, J; Magnani, JW; Marciante, KD; Pfeufer, A; Gharib, SA; Teumer, A; Li, M; Bis, JC; Rivadeneira, F; Aspelund, T; Köttgen, A; Johnson, T; Rice, K; Sie, MP; Wang, YA; Klopp, N; Fuchsberger, C; Wild, SH; Mateo Leach, I; Estrada, K; Volker, U; Wright, AF; Asselbergs, FW; Qu, J; Chakravarti, A; Sinner, MF; Kors, JA; Petersmann, A; Harris, TB; Soliman, EZ; Munroe, PB; Psaty, BM; Oostra, BA; Cupples, LA; Perz, S; de Boer, RA; Uitterlinden, AG; Völzke, H; Spector, TD; Liu, FY; Boerwinkle, E; Dominiczak, AF; Rotter, JI; van Herpen, G; Levy, D; Wichmann, HE; van Gilst, WH; Witteman, JC; Kroemer, HK; Kao, WH; Heckbert, SR; Meitinger, T; Hofman, A; Campbell, H; Folsom, AR; van Veldhuisen, DJ; Schwienbacher, C; O'Donnell, CJ; Volpato, CB; Caulfield, MJ; Connell, JM; Launer, L; Lu, X; Franke, L; Fehrmann, RS; te Meerman, G; Groen, HJ; Weersma, RK; Van den Berg, LH; Wijmenga, C; Ophoff, RA; Navis, G; Rudan, I; Snieder, H; Wilson, JF; Pramstaller, PP; Siscovick, DS; Wang, TJ; Gudnason, V; van Duijn, CM; Felix, SB; Fishman, GI; Jamshidi, Y; Stricker, BH; Samani, NJ; Kääb, S; Arking, DE «
Sotoodehnia, N; Isaacs, A; de Bakker, PI; Dörr, M; Newton-Cheh, C; Nolte, IM; van der Harst, P; Muller, M; Eijgelsheim, M; Alonso, A; Hicks, AA; Padmanabhan, S; Hayward, C; Smith, AV; Polasek, O; Giovannone, S; Fu, J; Magnani, JW; Marciante, KD; Pfeufer, A; Gharib, SA; Teumer, A; Li, M; Bis, JC; Rivadeneira, F; Aspelund, T; Köttgen, A; Johnson, T; Rice, K; Sie, MP; Wang, YA; Klopp, N; Fuchsberger, C; Wild, SH; Mateo Leach, I; Estrada, K; Volker, U; Wright, AF; Asselbergs, FW; Qu, J; Chakravarti,... »
Titel:: Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
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.
Zeitschriftentitel:: Nat Genet
Jahr:: 2010
Band / Volume:: 42
Heft / Issue:: 12
Seitenangaben Beitrag:: 1068-76
Sprache:: eng
Volltext / DOI:: doi:10.1038/ng.716
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/21076409
Print-ISSN:: 1061-4036
TUM Einrichtung:: Institut für Humangenetik
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