Replication of SCN5A associations with electrocardiographic traits in African Americans from clinical and epidemiologic studies

Janina M. Jeff, Kristin Brown-Gentry, Robert Goodloe, Marylyn D. Ritchie, Joshua C. Denny, Abel N. Kho, Loren L. Armstrong, Bob McClellan, Ping Mayo, Melissa Allen, Hailing Jin, Niloufar B. Gillani, Nathalie Schnetz-Boutaud, Holli H. Dilks, Melissa A. Basford, Jennifer A. Pacheco, Gail P. Jarvik, Rex L. Chisholm, Dan M. Roden, M. Geoffrey HayeDana C. Crawford

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 metaanalysis 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 Africandescent populations.

Original languageEnglish (US)
Title of host publicationApplications of Evolutionary Computation - 17th European Conference, EvoApplications 2014, Revised Selected Papers
EditorsAnna I. Esparcia-Alcázar
PublisherSpringer Verlag
Pages939-951
Number of pages13
ISBN (Electronic)9783662455227
DOIs
StatePublished - 2014
Event17th European Conference on Applications of Evolutionary Computation, EvoApplications 2014 - Granada, Spain
Duration: Apr 23 2014Apr 25 2014

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume8602
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

Other17th European Conference on Applications of Evolutionary Computation, EvoApplications 2014
CountrySpain
CityGranada
Period4/23/144/25/14

All Science Journal Classification (ASJC) codes

  • Theoretical Computer Science
  • Computer Science(all)

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    Jeff, J. M., Brown-Gentry, K., Goodloe, R., Ritchie, M. D., Denny, J. C., Kho, A. N., Armstrong, L. L., McClellan, B., Mayo, P., Allen, M., Jin, H., Gillani, N. B., Schnetz-Boutaud, N., Dilks, H. H., Basford, M. A., Pacheco, J. A., Jarvik, G. P., Chisholm, R. L., Roden, D. M., ... Crawford, D. C. (2014). Replication of SCN5A associations with electrocardiographic traits in African Americans from clinical and epidemiologic studies. In A. I. Esparcia-Alcázar (Ed.), Applications of Evolutionary Computation - 17th European Conference, EvoApplications 2014, Revised Selected Papers (pp. 939-951). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 8602). Springer Verlag. https://doi.org/10.1007/978-3-662-45523-4_76