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Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.

Floyd JS, Sitlani CM, Avery CL et al.

27958378 PubMed ID
GWAS Study Type
71857 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

FJ
Floyd JS
SC
Sitlani CM
AC
Avery CL
NR
Noordam R
LX
Li X
SA
Smith AV
GS
Gogarten SM
LJ
Li J
BL
Broer L
ED
Evans DS
TS
Trompet S
BJ
Brody JA
SJ
Stewart JD
EJ
Eicher JD
SA
Seyerle AA
RJ
Roach J
LL
Lange LA
LH
Lin HJ
KJ
Kors JA
HT
Harris TB
LR
Li-Gao R
SN
Sattar N
CS
Cummings SR
WK
Wiggins KL
NM
Napier MD
ST
Stürmer T
BJ
Bis JC
KK
Kerr KF
UA
Uitterlinden AG
TK
Taylor KD
SD
Stott DJ
DM
de Mutsert R
LL
Launer LJ
BE
Busch EL
MR
Méndez-Giráldez R
SN
Sotoodehnia N
SE
Soliman EZ
LY
Li Y
DQ
Duan Q
RF
Rosendaal FR
SP
Slagboom PE
WK
Wilhelmsen KC
RA
Reiner AP
CY
Chen YD
HS
Heckbert SR
KR
Kaplan RC
RK
Rice KM
JJ
Jukema JW
JA
Johnson AD
LY
Liu Y
MD
Mook-Kanamori DO
GV
Gudnason V
WJ
Wilson JG
RJ
Rotter JI
LC
Laurie CC
PB
Psaty BM
WE
Whitsel EA
CL
Cupples LA
SB
Stricker BH
Chapter II

Abstract

Summary of the research findings

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

2,095 European ancestry exposed individuals, 42,907 European ancestry unexposed individuals, 1,167 African American exposed individuals, 10,564 African American unexposed individuals, 794 Hispanic/Latino American exposed individuals, 14,330 Hispanic/Latino American unexposed individuals

Chapter III

Study Statistics

Key metrics and study information

71857
Total Participants
GWAS
Study Type
No
Replicated
African American or Afro-Caribbean, Hispanic or Latin American, European
Ancestry
U.S., Iceland, Netherlands, U.K., Republic of Ireland
Recruitment Country
Chapter IV

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