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Replication of SCN5A Associations with Electrocardiographic Traits in African Americans from Clinical and Epidemiologic Studies

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Applications of Evolutionary Computation (EvoApplications 2014)

Part of the book series: Lecture Notes in Computer Science ((LNTCS,volume 8602))

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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.

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Author information

Authors and Affiliations

  1. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Janina M. Jeff

  2. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232, USA

    Kristin Brown-Gentry, Robert Goodloe, Bob McClellan Jr., Ping Mayo, Melissa Allen, Hailing Jin, Niloufar B. Gillani, Nathalie Schnetz-Boutaud, Holli H. Dilks & Dana C. Crawford

  3. Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA

    Joshua C. Denny & Dan M. Roden

  4. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, 37232, USA

    Joshua C. Denny

  5. Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Abel N. Kho

  6. Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Loren L. Armstrong & M. Geoffrey Hayes

  7. Office of Personalized Medicine, Vanderbilt University, Nashville, TN, 37232, USA

    Melissa A. Basford & Dan M. Roden

  8. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Jennifer A. Pacheco & Rex L. Chisholm

  9. Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA

    Dan M. Roden

  10. Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA, 16802, USA

    Marylyn D. Ritchie

  11. University of Washington Medical Center, Seattle, WA, 98195, USA

    Gail P. Jarvik

Authors
  1. Janina M. Jeff
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  2. Kristin Brown-Gentry
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  6. Abel N. Kho
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  7. Loren L. Armstrong
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  9. Ping Mayo
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  18. Rex L. Chisholm
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  19. Dan M. Roden
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  20. M. Geoffrey Hayes
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  21. Dana C. Crawford
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Correspondence to Dana C. Crawford .

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Editors and Affiliations

  1. Depto. Estadística e Investigación, Universidad Politécnica de Valencia, Valencia, Spain

    Anna I. Esparcia-Alcázar

  2. University of Granada, Granada, Spain

    Antonio M. Mora

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Jeff, J.M. et al. (2014). Replication of SCN5A Associations with Electrocardiographic Traits in African Americans from Clinical and Epidemiologic Studies. In: Esparcia-Alcázar, A., Mora, A. (eds) Applications of Evolutionary Computation. EvoApplications 2014. Lecture Notes in Computer Science(), vol 8602. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45523-4_76

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