Genome-Wide Association Study of Electrocardiographic and Heart Rate Variability Traits: the Framingham Heart Study

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dc.contributor.author Newton-Cheh, Christopher en_US
dc.contributor.author Guo, Chao-Yu en_US
dc.contributor.author Wang, Thomas J en_US
dc.contributor.author O'Donnell, Christopher J en_US
dc.contributor.author Levy, Daniel en_US
dc.contributor.author Larson, Martin G en_US
dc.date.accessioned 2011-12-29T23:03:39Z
dc.date.available 2011-12-29T23:03:39Z
dc.date.copyright 2007 en_US
dc.date.issued 2007-9-19 en_US
dc.identifier.citation Newton-Cheh, Christopher, Chao-Yu Guo, Thomas J Wang, Christopher J O'Donnell, Daniel Levy, Martin G Larson. "Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study" BMC Medical Genetics 8 (Suppl 1): S7. (2007) en_US
dc.identifier.issn 1471-2350 en_US
dc.identifier.uri http://hdl.handle.net/2144/2629
dc.description.abstract BACKGROUND: Heritable electrocardiographic (ECG) and heart rate variability (HRV) measures, reflecting pacemaking, conduction, repolarization and autonomic function in the heart have been associated with risks for cardiac arrhythmias. Whereas several rare monogenic conditions with extreme phenotypes have been noted, few common genetic factors contributing to interindividual variability in ECG and HRV measures have been identified. We report the results of a community-based genomewide association study of six ECG and HRV intermediate traits. METHODS: Genotyping using Affymetrix 100K GeneChip was conducted on 1345 related Framingham Heart Study Original and Offspring cohort participants. We analyzed 1175 Original and Offspring participants with ECG data (mean age 52 years, 52% women) and 548 Offspring participants with HRV data (mean age 48 years, 51% women), in relation to 70,987 SNPs with minor allele frequency ≥ 0.10, call rate ≥ 80%, Hardy-Weinberg p-value ≥ 0.001. We used generalized estimating equations to test association of SNP alleles with multivariable-adjusted residuals for QT, RR, and PR intervals, the ratio of low frequency to high frequency power (LF/HFP), total power (TP) and the standard deviation of normal RR intervals (SDNN). RESULTS: Associations at p < 10-3 were found for 117 (QT), 105 (RR), 111 (PR), 102 (LF/HF), 121 (TP), and 102 (SDNN) SNPs. Several common variants in NOS1AP (4 SNPs with p-values < 10-3; lowest p-value, rs6683968, p = 1 × 10-4) were associated with adjusted QT residuals, consistent with our previously reported finding for NOS1AP in an unrelated sample of FHS Offspring and other cohorts. All results are publicly available at NCBI's dbGaP at. CONCLUSION: In the community-based Framingham Heart Study none of the ECG and HRV results individually attained genomewide significance. However, the presence of bona fide QT-associated SNPs among the top 117 results for QT duration supports the importance of efforts to validate top results from the reported scans. Finding genetic variants associated with ECG and HRV quantitative traits may identify novel genes and pathways implicated in arrhythmogenesis and allow for improved recognition of individuals at high risk for arrhythmias in the general population. en_US
dc.description.sponsorship National Institutes of Health (K23 N01-HC25195); Doris Duke Charitable Foundation Clinical Scientist Developement Award; Pfizer; National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2007 Newton-Cheh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Genome-Wide Association Study of Electrocardiographic and Heart Rate Variability Traits: the Framingham Heart Study en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2350-8-S1-S7 en_US
dc.identifier.pubmedid 17903306 en_US
dc.identifier.pmcid 1995612 en_US

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