Common variants in KCNN3 are associated with lone atrial fibrillation

PT Ellinor; KL Lunetta; NL Glazer; A Pfeufer; A Alonso; MK Chung; MF Sinner; PIW de Bakker; M Mueller; SA Lubitz; E Fox; D Darbar; NL Smith; JD Smith; RB Schnabel; EZ Soliman; KM Rice; DR Van Wagoner; BM Beckmann; Charlotte Noord; K Wang; GB Ehret; JI Rotter; SL Hazen; G Steinbeck; AV Smith; LJ (Lenore) Launer; TB Harris; S Makino; M Nelis; DJ Milan; S Perz; T Esko; A Kottgen; S Moebus; C Newton-Cheh; M Li; S Moehlenkamp; TJ Wang; WHL Kao; RS Vasan; MM Nothen; CA MacRae; Bruno Stricker; Bert Hofman; André Uitterlinden; D Levy; E Boerwinkle; A Metspalu; EJ Topol; A Chakravarti; V Gudnason; BM Psaty; DM Roden; T Meitinger; HE Wichmann; JCM Witteman; J Barnard; DE Arking; EJ Benjamin; SR Heckbert; S Kaab

doi:10.1038/ng.537

Common variants in KCNN3 are associated with lone atrial fibrillation

PT Ellinor, KL Lunetta, NL Glazer, A Pfeufer, A Alonso, MK Chung, MF Sinner, PIW de Bakker, M Mueller, SA Lubitz, E Fox, D Darbar, NL Smith, JD Smith, RB Schnabel, EZ Soliman, KM Rice, DR Van Wagoner, BM Beckmann, Charlotte NoordK Wang, GB Ehret, JI Rotter, SL Hazen, G Steinbeck, AV Smith, LJ (Lenore) Launer, TB Harris, S Makino, M Nelis, DJ Milan, S Perz, T Esko, A Kottgen, S Moebus, C Newton-Cheh, M Li, S Moehlenkamp, TJ Wang, WHL Kao, RS Vasan, MM Nothen, CA MacRae, Bruno Stricker, Bert Hofman, André Uitterlinden, D Levy, E Boerwinkle, A Metspalu, EJ Topol, A Chakravarti, V Gudnason, BM Psaty, DM Roden, T Meitinger, HE Wichmann, JCM Witteman, J Barnard, DE Arking, EJ Benjamin, SR Heckbert, S Kaab

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

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Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

Original language	Undefined/Unknown
Pages (from-to)	240-U36
Journal	Nature Genetics
Volume	42
Issue number	3
DOIs	https://doi.org/10.1038/ng.537
Publication status	Published - 2010

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10.1038/ng.537

http://hdl.handle.net/1765/28359

Cite this

Ellinor, PT., Lunetta, KL., Glazer, NL., Pfeufer, A., Alonso, A., Chung, MK., Sinner, MF., de Bakker, PIW., Mueller, M., Lubitz, SA., Fox, E., Darbar, D., Smith, NL., Smith, JD., Schnabel, RB., Soliman, EZ., Rice, KM., Van Wagoner, DR., Beckmann, BM., ... Kaab, S. (2010). Common variants in KCNN3 are associated with lone atrial fibrillation. Nature Genetics, 42(3), 240-U36. https://doi.org/10.1038/ng.537

@article{48c1a6c57495481b8d4c73c3a171a10f,

title = "Common variants in KCNN3 are associated with lone atrial fibrillation",

abstract = "Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.",

author = "PT Ellinor and KL Lunetta and NL Glazer and A Pfeufer and A Alonso and MK Chung and MF Sinner and {de Bakker}, PIW and M Mueller and SA Lubitz and E Fox and D Darbar and NL Smith and JD Smith and RB Schnabel and EZ Soliman and KM Rice and {Van Wagoner}, DR and BM Beckmann and Charlotte Noord and K Wang and GB Ehret and JI Rotter and SL Hazen and G Steinbeck and AV Smith and Launer, {LJ (Lenore)} and TB Harris and S Makino and M Nelis and DJ Milan and S Perz and T Esko and A Kottgen and S Moebus and C Newton-Cheh and M Li and S Moehlenkamp and TJ Wang and WHL Kao and RS Vasan and MM Nothen and CA MacRae and Bruno Stricker and Bert Hofman and Andr{\'e} Uitterlinden and D Levy and E Boerwinkle and A Metspalu and EJ Topol and A Chakravarti and V Gudnason and BM Psaty and DM Roden and T Meitinger and HE Wichmann and JCM Witteman and J Barnard and DE Arking and EJ Benjamin and SR Heckbert and S Kaab",

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Ellinor, PT, Lunetta, KL, Glazer, NL, Pfeufer, A, Alonso, A, Chung, MK, Sinner, MF, de Bakker, PIW, Mueller, M, Lubitz, SA, Fox, E, Darbar, D, Smith, NL, Smith, JD, Schnabel, RB, Soliman, EZ, Rice, KM, Van Wagoner, DR, Beckmann, BM, Noord, C, Wang, K, Ehret, GB, Rotter, JI, Hazen, SL, Steinbeck, G, Smith, AV, Launer, LJ, Harris, TB, Makino, S, Nelis, M, Milan, DJ, Perz, S, Esko, T, Kottgen, A, Moebus, S, Newton-Cheh, C, Li, M, Moehlenkamp, S, Wang, TJ, Kao, WHL, Vasan, RS, Nothen, MM, MacRae, CA, Stricker, B , Hofman, B , Uitterlinden, A, Levy, D, Boerwinkle, E, Metspalu, A, Topol, EJ, Chakravarti, A, Gudnason, V, Psaty, BM, Roden, DM, Meitinger, T, Wichmann, HE, Witteman, JCM, Barnard, J, Arking, DE, Benjamin, EJ, Heckbert, SR & Kaab, S 2010, 'Common variants in KCNN3 are associated with lone atrial fibrillation', Nature Genetics, vol. 42, no. 3, pp. 240-U36. https://doi.org/10.1038/ng.537

TY - JOUR

T1 - Common variants in KCNN3 are associated with lone atrial fibrillation

AU - Ellinor, PT

AU - Lunetta, KL

AU - Glazer, NL

AU - Pfeufer, A

AU - Alonso, A

AU - Chung, MK

AU - Sinner, MF

AU - de Bakker, PIW

AU - Mueller, M

AU - Lubitz, SA

AU - Fox, E

AU - Darbar, D

AU - Smith, NL

AU - Smith, JD

AU - Schnabel, RB

AU - Soliman, EZ

AU - Rice, KM

AU - Van Wagoner, DR

AU - Beckmann, BM

AU - Noord, Charlotte

AU - Wang, K

AU - Ehret, GB

AU - Rotter, JI

AU - Hazen, SL

AU - Steinbeck, G

AU - Smith, AV

AU - Launer, LJ (Lenore)

AU - Harris, TB

AU - Makino, S

AU - Nelis, M

AU - Milan, DJ

AU - Perz, S

AU - Esko, T

AU - Kottgen, A

AU - Moebus, S

AU - Newton-Cheh, C

AU - Li, M

AU - Moehlenkamp, S

AU - Wang, TJ

AU - Kao, WHL

AU - Vasan, RS

AU - Nothen, MM

AU - MacRae, CA

AU - Stricker, Bruno

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Levy, D

AU - Boerwinkle, E

AU - Metspalu, A

AU - Topol, EJ

AU - Chakravarti, A

AU - Gudnason, V

AU - Psaty, BM

AU - Roden, DM

AU - Meitinger, T

AU - Wichmann, HE

AU - Witteman, JCM

AU - Barnard, J

AU - Arking, DE

AU - Benjamin, EJ

AU - Heckbert, SR

AU - Kaab, S

PY - 2010

Y1 - 2010

N2 - Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

AB - Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

U2 - 10.1038/ng.537

DO - 10.1038/ng.537

M3 - Article

VL - 42

SP - 240-U36

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -