title: Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.
abstract: BACKGROUND
  The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.
  
  
  RESULTS
  We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)).
  
  
  CONCLUSIONS
  This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, 27514, USA. anne.butler@unc.edu
authors.forename: Anne M
authors.initials: AM
authors.lastname: Butler
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Erin N
authors.initials: EN
authors.lastname: Smith
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Eric A
authors.initials: EA
authors.lastname: Whitsel
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Berenson
authors.forename: Josh C
authors.initials: JC
authors.lastname: Bis
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Rajat
authors.initials: R
authors.lastname: Deo
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsueh
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Marian C
authors.initials: MC
authors.lastname: Limacher
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lubitz
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Marciante
authors.forename: Reena
authors.initials: R
authors.lastname: Mehra
authors.forename: Yan A
authors.initials: YA
authors.lastname: Meng
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Palmer
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: P Miguel
authors.initials: PM
authors.lastname: Quibrera
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: J Gustav
authors.initials: JG
authors.lastname: Smith
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: Sathanur R
authors.initials: SR
authors.lastname: Srinivasan
authors.forename: Zhu-ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.forename: Michele K
authors.initials: MK
authors.lastname: Evans
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.forename: Christy L
authors.initials: CL
authors.lastname: Avery
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics