title: Impact of ancestry and common genetic variants on QT interval in African Americans.
abstract: BACKGROUND
  Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.
  
  
  RESULTS
  First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN.
  
  
  CONCLUSIONS
  We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.
authors.affiliation: Department of Cardiology, Lund University, Skåne University Hospital, Sweden. gustav.smith@med.lu.se
authors.forename: J Gustav
authors.initials: JG
authors.lastname: Smith
authors.forename: Christy L
authors.initials: CL
authors.lastname: Avery
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Yan A
authors.initials: YA
authors.lastname: Meng
authors.forename: Erin N
authors.initials: EN
authors.lastname: Smith
authors.forename: Cameron
authors.initials: C
authors.lastname: Palmer
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Reena
authors.initials: R
authors.lastname: Mehra
authors.forename: Anne M
authors.initials: AM
authors.lastname: Butler
authors.forename: Taylor
authors.initials: T
authors.lastname: Young
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Berenson
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: J David
authors.initials: JD
authors.lastname: Curb
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsueh
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Marian C
authors.initials: MC
authors.lastname: Limacher
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.forename: P Miguel
authors.initials: PM
authors.lastname: Quibrera
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Solomon
authors.forename: Sathanur R
authors.initials: SR
authors.lastname: Srinivasan
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.forename: Robert
authors.initials: R
authors.lastname: Wallace
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Zhu-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.forename: Michele K
authors.initials: MK
authors.lastname: Evans
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Eric A
authors.initials: EA
authors.lastname: Whitsel
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D004562:Electrocardiography; D005260:Female; D005789:Genealogy and Heraldry; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics