Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2

Amanda A. Seyerle, Henry J. Lin, Stephanie M. Gogarten, Adrienne Stilp, Raul Méndez Giráldez, Elsayed Soliman, Antoine Baldassari, Mariaelisa Graff, Susan Heckbert, Kathleen F. Kerr, Charles Kooperberg, Carlos Rodriguez, Xiuqing Guo, Jie Yao, Nona Sotoodehnia, Kent D. Taylor, Eric A. Whitsel, Jerome I. Rotter, Cathy C. Laurie, Christy L. Avery

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies. Methods: Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results: were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results. Results: We identified a novel genome-wide association (P<5×10 -8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP. Conclusions: Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.

Original languageEnglish (US)
Pages (from-to)904-911
Number of pages8
JournalHeart
Volume104
Issue number11
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Hispanic Americans
Single Nucleotide Polymorphism
Population
Genome
Mortality
Genetic Models
Linkage Disequilibrium
Computational Biology
Atrial Fibrillation
Meta-Analysis
Heart Failure
Morbidity

Keywords

  • ECG/electrocardiogram
  • epidemiology
  • genetics
  • genome-wide association studies (GWAS)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Seyerle, A. A., Lin, H. J., Gogarten, S. M., Stilp, A., Méndez Giráldez, R., Soliman, E., ... Avery, C. L. (2018). Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2. Heart, 104(11), 904-911. https://doi.org/10.1136/heartjnl-2017-312045

Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2. / Seyerle, Amanda A.; Lin, Henry J.; Gogarten, Stephanie M.; Stilp, Adrienne; Méndez Giráldez, Raul; Soliman, Elsayed; Baldassari, Antoine; Graff, Mariaelisa; Heckbert, Susan; Kerr, Kathleen F.; Kooperberg, Charles; Rodriguez, Carlos; Guo, Xiuqing; Yao, Jie; Sotoodehnia, Nona; Taylor, Kent D.; Whitsel, Eric A.; Rotter, Jerome I.; Laurie, Cathy C.; Avery, Christy L.

In: Heart, Vol. 104, No. 11, 01.06.2018, p. 904-911.

Research output: Contribution to journalArticle

Seyerle, AA, Lin, HJ, Gogarten, SM, Stilp, A, Méndez Giráldez, R, Soliman, E, Baldassari, A, Graff, M, Heckbert, S, Kerr, KF, Kooperberg, C, Rodriguez, C, Guo, X, Yao, J, Sotoodehnia, N, Taylor, KD, Whitsel, EA, Rotter, JI, Laurie, CC & Avery, CL 2018, 'Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2', Heart, vol. 104, no. 11, pp. 904-911. https://doi.org/10.1136/heartjnl-2017-312045
Seyerle AA, Lin HJ, Gogarten SM, Stilp A, Méndez Giráldez R, Soliman E et al. Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2. Heart. 2018 Jun 1;104(11):904-911. https://doi.org/10.1136/heartjnl-2017-312045
Seyerle, Amanda A. ; Lin, Henry J. ; Gogarten, Stephanie M. ; Stilp, Adrienne ; Méndez Giráldez, Raul ; Soliman, Elsayed ; Baldassari, Antoine ; Graff, Mariaelisa ; Heckbert, Susan ; Kerr, Kathleen F. ; Kooperberg, Charles ; Rodriguez, Carlos ; Guo, Xiuqing ; Yao, Jie ; Sotoodehnia, Nona ; Taylor, Kent D. ; Whitsel, Eric A. ; Rotter, Jerome I. ; Laurie, Cathy C. ; Avery, Christy L. / Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2. In: Heart. 2018 ; Vol. 104, No. 11. pp. 904-911.
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abstract = "Objective: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies. Methods: Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results: were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results. Results: We identified a novel genome-wide association (P<5×10 -8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP. Conclusions: Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.",
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T1 - Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2

AU - Seyerle, Amanda A.

AU - Lin, Henry J.

AU - Gogarten, Stephanie M.

AU - Stilp, Adrienne

AU - Méndez Giráldez, Raul

AU - Soliman, Elsayed

AU - Baldassari, Antoine

AU - Graff, Mariaelisa

AU - Heckbert, Susan

AU - Kerr, Kathleen F.

AU - Kooperberg, Charles

AU - Rodriguez, Carlos

AU - Guo, Xiuqing

AU - Yao, Jie

AU - Sotoodehnia, Nona

AU - Taylor, Kent D.

AU - Whitsel, Eric A.

AU - Rotter, Jerome I.

AU - Laurie, Cathy C.

AU - Avery, Christy L.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Objective: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies. Methods: Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results: were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results. Results: We identified a novel genome-wide association (P<5×10 -8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP. Conclusions: Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.

AB - Objective: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies. Methods: Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results: were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results. Results: We identified a novel genome-wide association (P<5×10 -8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP. Conclusions: Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.

KW - ECG/electrocardiogram

KW - epidemiology

KW - genetics

KW - genome-wide association studies (GWAS)

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