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dc.contributor.authorNewton-Cheh, Christopheren_US
dc.contributor.authorGuo, Chao-Yuen_US
dc.contributor.authorWang, Thomas Jen_US
dc.contributor.authorO'Donnell, Christopher Jen_US
dc.contributor.authorLevy, Danielen_US
dc.contributor.authorLarson, Martin Gen_US
dc.date.accessioned2011-12-29T23:03:39Z
dc.date.available2011-12-29T23:03:39Z
dc.date.copyright2007en_US
dc.date.issued2007-9-19en_US
dc.identifier.citationNewton-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.issn1471-2350en_US
dc.identifier.urihttp://hdl.handle.net/2144/2629
dc.description.abstractBACKGROUND: 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.sponsorshipNational 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.isoenen_US
dc.publisherBioMed Centralen_US
dc.rightsCopyright 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.urihttp://creativecommons.org/licenses/by/2.0en_US
dc.titleGenome-Wide Association Study of Electrocardiographic and Heart Rate Variability Traits: the Framingham Heart Studyen_US
dc.typearticleen_US
dc.identifier.doi10.1186/1471-2350-8-S1-S7en_US
dc.identifier.pubmedid17903306en_US
dc.identifier.pmcid1995612en_US


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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.
Except where otherwise noted, this item's license is described as 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.