Genome-Wide Association Studies of the PR Interval in African Americans.

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Genome-Wide Association Studies of the PR Interval in African Americans. / Smith, Gustav; Magnani, Jared W; Palmer, Cameron; Meng, Yan A; Soliman, Elsayed Z; Musani, Solomon K; Kerr, Kathleen F; Schnabel, Renate B; Lubitz, Steven A; Sotoodehnia, Nona; Redline, Susan; Pfeufer, Arne; Müller, Martina; Evans, Daniel S; Nalls, Michael A; Liu, Yongmei; Newman, Anne B; Zonderman, Alan B; Evans, Michele K; Deo, Rajat; Ellinor, Patrick T; Paltoo, Dina N; Newton-Cheh, Christopher; Benjamin, Emelia J; Mehra, Reena; Alonso, Alvaro; Heckbert, Susan R; Fox, Ervin R.

I: PLoS Genetics, Vol. 7, Nr. 2, e1001304, 2011.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Smith, G, Magnani, JW, Palmer, C, Meng, YA, Soliman, EZ, Musani, SK, Kerr, KF, Schnabel, RB, Lubitz, SA, Sotoodehnia, N, Redline, S, Pfeufer, A, Müller, M, Evans, DS, Nalls, MA, Liu, Y, Newman, AB, Zonderman, AB, Evans, MK, Deo, R, Ellinor, PT, Paltoo, DN, Newton-Cheh, C, Benjamin, EJ, Mehra, R, Alonso, A, Heckbert, SR & Fox, ER 2011, 'Genome-Wide Association Studies of the PR Interval in African Americans.', PLoS Genetics, vol. 7, nr. 2, e1001304. https://doi.org/10.1371/journal.pgen.1001304

APA

Smith, G., Magnani, J. W., Palmer, C., Meng, Y. A., Soliman, E. Z., Musani, S. K., ... Fox, E. R. (2011). Genome-Wide Association Studies of the PR Interval in African Americans. PLoS Genetics, 7(2), [e1001304]. https://doi.org/10.1371/journal.pgen.1001304

CBE

Smith G, Magnani JW, Palmer C, Meng YA, Soliman EZ, Musani SK, Kerr KF, Schnabel RB, Lubitz SA, Sotoodehnia N, Redline S, Pfeufer A, Müller M, Evans DS, Nalls MA, Liu Y, Newman AB, Zonderman AB, Evans MK, Deo R, Ellinor PT, Paltoo DN, Newton-Cheh C, Benjamin EJ, Mehra R, Alonso A, Heckbert SR, Fox ER. 2011. Genome-Wide Association Studies of the PR Interval in African Americans. PLoS Genetics. 7(2). https://doi.org/10.1371/journal.pgen.1001304

MLA

Vancouver

Author

Smith, Gustav ; Magnani, Jared W ; Palmer, Cameron ; Meng, Yan A ; Soliman, Elsayed Z ; Musani, Solomon K ; Kerr, Kathleen F ; Schnabel, Renate B ; Lubitz, Steven A ; Sotoodehnia, Nona ; Redline, Susan ; Pfeufer, Arne ; Müller, Martina ; Evans, Daniel S ; Nalls, Michael A ; Liu, Yongmei ; Newman, Anne B ; Zonderman, Alan B ; Evans, Michele K ; Deo, Rajat ; Ellinor, Patrick T ; Paltoo, Dina N ; Newton-Cheh, Christopher ; Benjamin, Emelia J ; Mehra, Reena ; Alonso, Alvaro ; Heckbert, Susan R ; Fox, Ervin R. / Genome-Wide Association Studies of the PR Interval in African Americans. I: PLoS Genetics. 2011 ; Vol. 7, Nr. 2.

RIS

TY - JOUR

T1 - Genome-Wide Association Studies of the PR Interval in African Americans.

AU - Smith, Gustav

AU - Magnani, Jared W

AU - Palmer, Cameron

AU - Meng, Yan A

AU - Soliman, Elsayed Z

AU - Musani, Solomon K

AU - Kerr, Kathleen F

AU - Schnabel, Renate B

AU - Lubitz, Steven A

AU - Sotoodehnia, Nona

AU - Redline, Susan

AU - Pfeufer, Arne

AU - Müller, Martina

AU - Evans, Daniel S

AU - Nalls, Michael A

AU - Liu, Yongmei

AU - Newman, Anne B

AU - Zonderman, Alan B

AU - Evans, Michele K

AU - Deo, Rajat

AU - Ellinor, Patrick T

AU - Paltoo, Dina N

AU - Newton-Cheh, Christopher

AU - Benjamin, Emelia J

AU - Mehra, Reena

AU - Alonso, Alvaro

AU - Heckbert, Susan R

AU - Fox, Ervin R

PY - 2011

Y1 - 2011

N2 - The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10(-8)) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1-6.1, p = 3×10(-23)). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8-3.0, p = 3×10(-16)) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.

AB - The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10(-8)) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1-6.1, p = 3×10(-23)). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8-3.0, p = 3×10(-16)) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.

U2 - 10.1371/journal.pgen.1001304

DO - 10.1371/journal.pgen.1001304

M3 - Article

VL - 7

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7404

IS - 2

M1 - e1001304

ER -