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GWAS Study

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

Sotoodehnia N, Isaacs A, de Bakker PI et al.

21076409 PubMed ID
GWAS Study Type
47577 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

SN
Sotoodehnia N
IA
Isaacs A
DB
de Bakker PI
DM
Dörr M
NC
Newton-Cheh C
NI
Nolte IM
VD
van der Harst P
MM
Müller M
EM
Eijgelsheim M
AA
Alonso A
HA
Hicks AA
PS
Padmanabhan S
HC
Hayward C
SA
Smith AV
PO
Polasek O
GS
Giovannone S
FJ
Fu J
MJ
Magnani JW
MK
Marciante KD
PA
Pfeufer A
GS
Gharib SA
TA
Teumer A
LM
Li M
BJ
Bis JC
RF
Rivadeneira F
AT
Aspelund T
KA
Köttgen A
JT
Johnson T
RK
Rice K
SM
Sie MP
WY
Wang YA
KN
Klopp N
FC
Fuchsberger C
WS
Wild SH
ML
Mateo Leach I
EK
Estrada K
VU
Völker U
WA
Wright AF
AF
Asselbergs FW
QJ
Qu J
CA
Chakravarti A
SM
Sinner MF
KJ
Kors JA
PA
Petersmann A
HT
Harris TB
SE
Soliman EZ
MP
Munroe PB
PB
Psaty BM
OB
Oostra BA
CL
Cupples LA
PS
Perz S
DB
de Boer RA
UA
Uitterlinden AG
VH
Völzke H
ST
Spector TD
LF
Liu FY
BE
Boerwinkle E
DA
Dominiczak AF
RJ
Rotter JI
VH
van Herpen G
LD
Levy D
WH
Wichmann HE
VG
van Gilst WH
WJ
Witteman JC
KH
Kroemer HK
KW
Kao WH
HS
Heckbert SR
MT
Meitinger T
HA
Hofman A
CH
Campbell H
FA
Folsom AR
VV
van Veldhuisen DJ
SC
Schwienbacher C
OC
O'Donnell CJ
VC
Volpato CB
CM
Caulfield MJ
CJ
Connell JM
LL
Launer L
LX
Lu X
FL
Franke L
FR
Fehrmann RS
TM
te Meerman G
GH
Groen HJ
WR
Weersma RK
VD
van den Berg LH
WC
Wijmenga C
OR
Ophoff RA
NG
Navis G
RI
Rudan I
SH
Snieder H
WJ
Wilson JF
PP
Pramstaller PP
SD
Siscovick DS
WT
Wang TJ
GV
Gudnason V
VD
van Duijn CM
FS
Felix SB
FG
Fishman GI
JY
Jamshidi Y
SB
Stricker BH
SN
Samani NJ
KS
Kääb S
AD
Arking DE
Chapter II

Abstract

Summary of the research findings

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.

39,717 European ancestry individuals, 690 Orcadian individuals

Chapter III

Study Statistics

Key metrics and study information

47577
Total Participants
GWAS
Study Type
Yes
Replicated
7,170 European ancestry individuals
Replication Participants
European
Ancestry
Netherlands, U.S., Italy, Germany, U.K., Croatia
Recruitment Country
Chapter IV

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