title: Generalization of variants identified by genome-wide association studies for electrocardiographic traits in African Americans.
abstract: Electrocardiographic (ECG) measurements vary by ancestry. Genome-wide association studies (GWAS) have identified loci that contribute to ECG measurements; however, most are performed in Europeans collected from population-based cohorts or surveys. The strongest associations reported are in NOS1AP with QT interval and SCN10A with PR and QRS durations. The extent to which these associations can be generalized to African Americans has yet to be determined. Using electronic medical records, PR and QT intervals, QRS duration, and heart rate were determined in 455 African Americans as part of the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project. We tested for an association between these ECG traits and >930K SNPs. We identified a total 36 novel associations with PR interval, QRS duration, QT interval, and heart rate at p < 1.0 × 10(-6). Using published GWAS data, we compared our results with those previously identified in other populations. Five associations originally identified in other populations generalized with respect to statistical significance and direction of effect. A total of 43 associations have a consistent direction of effect with European and/or Asian populations. This work provides a catalogue of generalized versus nongeneralized associations, a necessary step in prioritizing GWAS-identified regions for further fine-mapping in diverse populations.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Jeff
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Ramirez
authors.forename: David
authors.initials: D
authors.lastname: Crosslin
authors.forename: Loren
authors.initials: L
authors.lastname: Armstrong
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wolf
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pacheco
authors.forename: Rex L
authors.initials: RL
authors.lastname: Chisholm
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D002874:Chromosome Mapping; D004562:Electrocardiography; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D044465:White People / Q000235:genetics
keywords: African Americans; Electrocardiography; GWAS; electronic medical records; generalization