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Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then. Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation.
Poster Abstract PresentationsSession Title: Genetics

Abstract P252: Generalization and Fine Mapping of PR Interval Loci in Hispanics: The Population Architecture Using Genomics and Epidemiology (PAGE) Study

Amanda A Seyerle, Christina Wassel, Cara L Carty, Myriam Fornage, Suzette J Bielinski, Steve Buyske, Mercedes R Carnethon, Dana C Crawford, David J Duggan, Jian Gong, Susan R Heckbert, Lucia A Hindorff, Janina M Jeff, Donald M Lloyd-Jones, Peter M Okin, Marco V Perez, Bruce M Psaty, Jerome I Rotter, Sanjiv J Shah, Ralph V Shohet, Elsayed Z Soliman, Nona Sotoodehnia, Chunyuan Wu, Charles Kooperberg, Christy L Avery
Circulation. 2014;129:AP252
Amanda A Seyerle
Univ of North Carolina at Chapel Hill, Chapel Hill, NC
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Christina Wassel
Univ of California San Diego, San Diego, CA
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Cara L Carty
Fred Hutchinson Cancer Rsch Cntr, Seattle, WA
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Myriam Fornage
Univ of Texas Health Sciences Cntr, Houston, TX
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Suzette J Bielinski
Mayo Clinic, Rochester, MN
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Steve Buyske
Rutgers Univ, Piscataway, NJ
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Mercedes R Carnethon
Northwestern Univ Feinberg Sch of Medicine, Chicago, IL
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Dana C Crawford
Vanderbilt Univ, Nashville, TN
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David J Duggan
Translational Genomics Rsch Institute, Pheonix, AZ
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Jian Gong
Fred Hutchinson Cancer Rsch Cntr, Seattle, WA
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Susan R Heckbert
Univ of Washington, Seattle, WA
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Lucia A Hindorff
National Human Genome Rsch Institute, Bethesda, MD
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Janina M Jeff
Mount Sinai Sch of Medicine, New York, NY
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Donald M Lloyd-Jones
Massachusetts General Hosp, Boston, MA
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Peter M Okin
Weill Cornell Med College, New York, NY
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Marco V Perez
Stanford Univ, Stanford, CA
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Bruce M Psaty
Univ of Washington, Seattle, WA
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Jerome I Rotter
Cedars-Sinai Med Cntr, Los Angeles, CA
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Sanjiv J Shah
Northwestern Univ Feinberg Sch of Medicine, Chicago, IL
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Ralph V Shohet
Univ of Hawaii, Honolulu, HI
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Elsayed Z Soliman
Wake Forest Sch of Medicine, Winston-Salem, NC
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Nona Sotoodehnia
Univ of Washington, Seattle, WA
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Chunyuan Wu
Fred Hutchinson Cancer Rsch Cntr, Seattle, WA
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Charles Kooperberg
Fred Hutchinson Cancer Rsch Cntr, Seattle, WA
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Christy L Avery
Univ of North Carolina at Chapel Hill, Chapel Hill, NC
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Abstract

PR interval (PR) prolongation is a predictor of atrial fibrillation, a common cardiac arrhythmia, and is an established risk factor for pacemaker implantation, heart failure, stroke, and all-cause mortality. Previous genome-wide association studies in European (EU) and African (AA) descent populations have identified multiple loci associated with PR. However, it is unclear whether these loci are relevant in other racial groups, including Hispanic/Latinos (HL). Extending studies to include admixed populations such as HL also provides the potential to narrow regions associated with PR and identify population specific variants. Therefore, we evaluated 1,135 SNPs from four previously identified PR loci (SCN5A, SCN10A, CAV1-CAV2, and TBX5-TBX3), fine-mapped on the Illumina Metabochip for association with PR. Associations were examined using linear regression assuming an additive genetic model and adjusting for global ancestry and clinical covariates (age, sex, RR interval, body mass index, height, systolic blood pressure) in 11,800 HL participants from participating studies of the Population Architecture using Genomics and Epidemiology (PAGE) consortia. Three of the four loci (SCN5A, SCN10A, and CAV1-CAV2) generalized to HL populations (P<7.1E-4 based on the number of SNPs correlated at r2>0.2 with EU-identified index SNPs). At each of these loci, we identified SNPs with stronger evidence of association with PR than the EU-identified index SNP when examined in the HL population (SCN5A: rs7374540; SCN10A: rs6801957; CAV-CAV2: rs717957). Conditional analyses also identified two additional independent SNPs at each of the three generalized loci (SCN5A: rs3796387, rs9861242; SCN10A: rs10428132, rs7433723; CAV1-CAV2: rs3801995, rs3807994), representing potential secondary signals. Furthermore, linkage disequilibrium (LD) patterns in Hispanics enabled the narrowing of the regions flanking the EU-identified index SNPs. For example, at the CAV1-CAV2 locus, HL LD patterns indicated that seven SNPs were in LD with rs3807989, the EU-identified index SNP, compared to 17 SNPs that were in LD with rs3807989 when applying EU LD patterns, reducing the size of the region by 71 kilobases. Finally, we examined evidence for population specific signals outside of the specific regions identified in EU populations which were associated with PR in Hispanics by focusing on SNPs uncorrelated with the EU index signals. At all four loci, multiple SNPs had evidence of association independent of the signals examined based on EU results. In conclusion, the same genetic loci that influence PR in European descent populations are also important in Hispanic populations, although we detected evidence for population specific SNPs. These results emphasize the importance of examining genetic associations in diverse populations in order to narrow the genomic interval for future functional interrogation.

  • Genetics
  • Electrocardiography
  • Author Disclosures: A.A. Seyerle: None. C. Wassel: None. C.L. Carty: None. M. Fornage: None. S.J. Bielinski: None. S. Buyske: None. M.R. Carnethon: None. D.C. Crawford: None. D.J. Duggan: None. J. Gong: None. S.R. Heckbert: None. L.A. Hindorff: None. J.M. Jeff: None. D.M. Lloyd-Jones: None. P.M. Okin: None. M.V. Perez: None. B.M. Psaty: None. J.I. Rotter: None. S.J. Shah: None. R.V. Shohet: None. E.Z. Soliman: None. N. Sotoodehnia: None. C. Wu: None. C. Kooperberg: None. C.L. Avery: None.

  • © 2014 by American Heart Association, Inc.
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March 25, 2014, Volume 129, Issue Suppl 1
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    Abstract P252: Generalization and Fine Mapping of PR Interval Loci in Hispanics: The Population Architecture Using Genomics and Epidemiology (PAGE) Study
    Amanda A Seyerle, Christina Wassel, Cara L Carty, Myriam Fornage, Suzette J Bielinski, Steve Buyske, Mercedes R Carnethon, Dana C Crawford, David J Duggan, Jian Gong, Susan R Heckbert, Lucia A Hindorff, Janina M Jeff, Donald M Lloyd-Jones, Peter M Okin, Marco V Perez, Bruce M Psaty, Jerome I Rotter, Sanjiv J Shah, Ralph V Shohet, Elsayed Z Soliman, Nona Sotoodehnia, Chunyuan Wu, Charles Kooperberg and Christy L Avery
    Circulation. 2014;129:AP252, originally published March 19, 2014

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    Abstract P252: Generalization and Fine Mapping of PR Interval Loci in Hispanics: The Population Architecture Using Genomics and Epidemiology (PAGE) Study
    Amanda A Seyerle, Christina Wassel, Cara L Carty, Myriam Fornage, Suzette J Bielinski, Steve Buyske, Mercedes R Carnethon, Dana C Crawford, David J Duggan, Jian Gong, Susan R Heckbert, Lucia A Hindorff, Janina M Jeff, Donald M Lloyd-Jones, Peter M Okin, Marco V Perez, Bruce M Psaty, Jerome I Rotter, Sanjiv J Shah, Ralph V Shohet, Elsayed Z Soliman, Nona Sotoodehnia, Chunyuan Wu, Charles Kooperberg and Christy L Avery
    Circulation. 2014;129:AP252, originally published March 19, 2014
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