Genome-wide association study of PR interval

A Pfeufer; Charlotte Noord; KD Marciante; DE Arking; MG Larson; AV Smith; KV Tarasov; M (Majon) Muller; N Sotoodehnia; MF Sinner; Germaine Verwoert; M Li; WHL Kao; A Kottgen; J Coresh; JC Bis; BM Psaty; K Rice; JI Rotter; Fernando Rivadeneira; Bert Hofman; Jan Kors; Bruno Stricker; André Uitterlinden; Cornelia Duijn; BM Beckmann; W Sauter; C Gieger; SA Lubitz; C Newton-Cheh; TJ Wang; JW Magnani; RB Schnabel; MK Chung; J Barnard; JD Smith; DR Van Wagoner; RS Vasan; T Aspelund; G Eiriksdottir; TB Harris; LJ (Lenore) Launer; SS Najjar; E Lakatta; D Schlessinger; M Uda; GR Abecasis; B Muller-Myhsok; GB Ehret; E Boerwinkle; A Chakravarti; EZ Soliman; KL Lunetta; S Perz; HE Wichmann; T Meitinger; D Levy; V Gudnason; PT Ellinor; S Sanna; S Kaab; JCM Witteman; A Alonso; EJ Benjamin; SR Heckbert

doi:10.1038/ng.517

Genome-wide association study of PR interval

A Pfeufer, Charlotte Noord, KD Marciante, DE Arking, MG Larson, AV Smith, KV Tarasov, M (Majon) Muller, N Sotoodehnia, MF Sinner, Germaine Verwoert, M Li, WHL Kao, A Kottgen, J Coresh, JC Bis, BM Psaty, K Rice, JI Rotter, Fernando RivadeneiraBert Hofman, Jan Kors, Bruno Stricker, André Uitterlinden, Cornelia Duijn, BM Beckmann, W Sauter, C Gieger, SA Lubitz, C Newton-Cheh, TJ Wang, JW Magnani, RB Schnabel, MK Chung, J Barnard, JD Smith, DR Van Wagoner, RS Vasan, T Aspelund, G Eiriksdottir, TB Harris, LJ (Lenore) Launer, SS Najjar, E Lakatta, D Schlessinger, M Uda, GR Abecasis, B Muller-Myhsok, GB Ehret, E Boerwinkle, A Chakravarti, EZ Soliman, KL Lunetta, S Perz, HE Wichmann, T Meitinger, D Levy, V Gudnason, PT Ellinor, S Sanna, S Kaab, JCM Witteman, A Alonso, EJ Benjamin, SR Heckbert

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

Original language	Undefined/Unknown
Pages (from-to)	153-U89
Journal	Nature Genetics
Volume	42
Issue number	2
DOIs	https://doi.org/10.1038/ng.517
Publication status	Published - 2010

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Access to Document

10.1038/ng.517

http://hdl.handle.net/1765/28298

Cite this

Pfeufer, A., Noord, C., Marciante, KD., Arking, DE., Larson, MG., Smith, AV., Tarasov, KV., Muller, M., Sotoodehnia, N., Sinner, MF., Verwoert, G., Li, M., Kao, WHL., Kottgen, A., Coresh, J., Bis, JC., Psaty, BM., Rice, K., Rotter, JI., ... Heckbert, SR. (2010). Genome-wide association study of PR interval. Nature Genetics, 42(2), 153-U89. https://doi.org/10.1038/ng.517

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abstract = "The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.",

author = "A Pfeufer and Charlotte Noord and KD Marciante and DE Arking and MG Larson and AV Smith and KV Tarasov and Muller, {M (Majon)} and N Sotoodehnia and MF Sinner and Germaine Verwoert and M Li and WHL Kao and A Kottgen and J Coresh and JC Bis and BM Psaty and K Rice and JI Rotter and Fernando Rivadeneira and Bert Hofman and Jan Kors and Bruno Stricker and Andr{\'e} Uitterlinden and Cornelia Duijn and BM Beckmann and W Sauter and C Gieger and SA Lubitz and C Newton-Cheh and TJ Wang and JW Magnani and RB Schnabel and MK Chung and J Barnard and JD Smith and {Van Wagoner}, DR and RS Vasan and T Aspelund and G Eiriksdottir and TB Harris and Launer, {LJ (Lenore)} and SS Najjar and E Lakatta and D Schlessinger and M Uda and GR Abecasis and B Muller-Myhsok and GB Ehret and E Boerwinkle and A Chakravarti and EZ Soliman and KL Lunetta and S Perz and HE Wichmann and T Meitinger and D Levy and V Gudnason and PT Ellinor and S Sanna and S Kaab and JCM Witteman and A Alonso and EJ Benjamin and SR Heckbert",

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Pfeufer, A, Noord, C, Marciante, KD, Arking, DE, Larson, MG, Smith, AV, Tarasov, KV, Muller, M, Sotoodehnia, N, Sinner, MF, Verwoert, G, Li, M, Kao, WHL, Kottgen, A, Coresh, J, Bis, JC, Psaty, BM, Rice, K, Rotter, JI, Rivadeneira, F , Hofman, B , Kors, J , Stricker, B , Uitterlinden, A, Duijn, C, Beckmann, BM, Sauter, W, Gieger, C, Lubitz, SA, Newton-Cheh, C, Wang, TJ, Magnani, JW, Schnabel, RB, Chung, MK, Barnard, J, Smith, JD, Van Wagoner, DR, Vasan, RS, Aspelund, T, Eiriksdottir, G, Harris, TB, Launer, LJ, Najjar, SS, Lakatta, E, Schlessinger, D, Uda, M, Abecasis, GR, Muller-Myhsok, B, Ehret, GB, Boerwinkle, E, Chakravarti, A, Soliman, EZ, Lunetta, KL, Perz, S, Wichmann, HE, Meitinger, T, Levy, D, Gudnason, V, Ellinor, PT, Sanna, S, Kaab, S, Witteman, JCM, Alonso, A, Benjamin, EJ & Heckbert, SR 2010, 'Genome-wide association study of PR interval', Nature Genetics, vol. 42, no. 2, pp. 153-U89. https://doi.org/10.1038/ng.517

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T1 - Genome-wide association study of PR interval

AU - Pfeufer, A

AU - Noord, Charlotte

AU - Marciante, KD

AU - Arking, DE

AU - Larson, MG

AU - Smith, AV

AU - Tarasov, KV

AU - Muller, M (Majon)

AU - Sotoodehnia, N

AU - Sinner, MF

AU - Verwoert, Germaine

AU - Li, M

AU - Kao, WHL

AU - Kottgen, A

AU - Coresh, J

AU - Bis, JC

AU - Psaty, BM

AU - Rice, K

AU - Rotter, JI

AU - Rivadeneira, Fernando

AU - Hofman, Bert

AU - Kors, Jan

AU - Stricker, Bruno

AU - Uitterlinden, André

AU - Duijn, Cornelia

AU - Beckmann, BM

AU - Sauter, W

AU - Gieger, C

AU - Lubitz, SA

AU - Newton-Cheh, C

AU - Wang, TJ

AU - Magnani, JW

AU - Schnabel, RB

AU - Chung, MK

AU - Barnard, J

AU - Smith, JD

AU - Van Wagoner, DR

AU - Vasan, RS

AU - Aspelund, T

AU - Eiriksdottir, G

AU - Harris, TB

AU - Launer, LJ (Lenore)

AU - Najjar, SS

AU - Lakatta, E

AU - Schlessinger, D

AU - Uda, M

AU - Abecasis, GR

AU - Muller-Myhsok, B

AU - Ehret, GB

AU - Boerwinkle, E

AU - Chakravarti, A

AU - Soliman, EZ

AU - Lunetta, KL

AU - Perz, S

AU - Wichmann, HE

AU - Meitinger, T

AU - Levy, D

AU - Gudnason, V

AU - Ellinor, PT

AU - Sanna, S

AU - Kaab, S

AU - Witteman, JCM

AU - Alonso, A

AU - Benjamin, EJ

AU - Heckbert, SR

PY - 2010

Y1 - 2010

N2 - The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

AB - The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

U2 - 10.1038/ng.517

DO - 10.1038/ng.517

M3 - Article

C2 - 20062060

SN - 1061-4036

VL - 42

SP - 153-U89

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -