Author:
Butler Anne M.,Yin Xiaoyan,Evans Daniel S.,Nalls Michael A.,Smith Erin N.,Tanaka Toshiko,Li Guo,Buxbaum Sarah G.,Whitsel Eric A.,Alonso Alvaro,Arking Dan E.,Benjamin Emelia J.,Berenson Gerald S.,Bis Josh C.,Chen Wei,Deo Rajat,Ellinor Patrick T.,Heckbert Susan R.,Heiss Gerardo,Hsueh Wen-Chi,Keating Brendan J.,Kerr Kathleen F.,Li Yun,Limacher Marian C.,Liu Yongmei,Lubitz Steven A.,Marciante Kristin D.,Mehra Reena,Meng Yan A.,Newman Anne B.,Newton-Cheh Christopher,North Kari E.,Palmer Cameron D.,Psaty Bruce M.,Quibrera P. Miguel,Redline Susan,Reiner Alex P.,Rotter Jerome I.,Schnabel Renate B.,Schork Nicholas J.,Singleton Andrew B.,Smith J. Gustav,Soliman Elsayed Z.,Srinivasan Sathanur R.,Zhang Zhu-ming,Zonderman Alan B.,Ferrucci Luigi,Murray Sarah S.,Evans Michele K.,Sotoodehnia Nona,Magnani Jared W.,Avery Christy L.
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.
Methods and 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics(clinical),Cardiology and Cardiovascular Medicine,Genetics