title: Replication ofSCN5AAssociations with Electrocardio-graphic Traits in African Americans from Clinical and Epidemiologic Studies.
abstract: The NAv1.5 sodium channel α subunit is the predominant α-subunit expressed in the heart and is associated with cardiac arrhythmias. We tested five previously identifiedSCN5Avariants (rs7374138, rs7637849, rs7637849, rs7629265, and rs11129796) for an association with PR interval and QRS duration in two unique study populations: the Third National Health and Nutrition Examination Survey (NHANES III, n= 552) accessed by the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) and a combined dataset (n= 455) from two biobanks linked to electronic medical records from Vanderbilt University (BioVU) and Northwestern University (NUgene) as part of the electronic Medical Records & Genomics (eMERGE) network. A meta-analysis including all three study populations (n~4,000) suggests that eightSCN5Aassociations were significant for both QRS duration and PR interval (p<5.0E-3) with little evidence for heterogeneity across the study populations. These results suggest that publishedSCN5Aassociations replicate across different study designs in a meta-analysis and represent an important first step in utility of multiple study designs for genetic studies and the identification/characterization of genetic variants associated with ECG traits in African-descent populations.
authors.affiliation: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Jeff
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Brown-Gentry
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodloe
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.affiliation: Office of Personalized Medicine, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Loren L
authors.initials: LL
authors.lastname: Armstrong
authors.affiliation: Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: McClellan
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Mayo
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Allen
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195, USA.
authors.forename: Hailing
authors.initials: H
authors.lastname: Jin
authors.forename: Niloufar B
authors.initials: NB
authors.lastname: Gillani
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schnetz-Boutaud
authors.forename: Holli H
authors.initials: HH
authors.lastname: Dilks
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pacheco
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
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
keywords: African Americans; NHANES; eMERGE; electrocardiographic traits; electronic medical records; epidemiology; genetic association study