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Replication of SCN5A Associations with Electrocardio-graphic Traits in African Americans from Clinical and Epidemiologic Studies.

Author information

1
Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
2
Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
3
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
4
Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37232, USA.
5
Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
6
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
7
Office of Personalized Medicine, Vanderbilt University, Nashville, TN 37232, USA.
8
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
9
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
10
Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.
11
University of Washington Medical Center, Seattle, WA 98195, USA.

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 identified SCN5A variants (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 eight SCN5A associations 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 published SCN5A associations 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.

KEYWORDS:

African Americans; NHANES; eMERGE; electrocardiographic traits; electronic medical records; epidemiology; genetic association study

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