Standard
Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval. / Lin, Honghuang; van Setten, Jessica; Smith, Albert V; Bihlmeyer, Nathan A; Warren, Helen R; Brody, Jennifer A; Radmanesh, Farid; Hall, Leanne; Grarup, Niels; Müller-Nurasyid, Martina; Boutin, Thibaud; Verweij, Niek; Lin, Henry J; Li-Gao, Ruifang; van den Berg, Marten E; Marten, Jonathan; Weiss, Stefan; Prins, Bram P; Haessler, Jeffrey; Lyytikäinen, Leo-Pekka; Mei, Hao; Harris, Tamara B; Launer, Lenore J; Li, Man; Alonso, Alvaro; Soliman, Elsayed Z; Connell, John M; Huang, Paul L; Weng, Lu-Chen; Jameson, Heather S; Hucker, William; Hanley, Alan; Tucker, Nathan R; Chen, Yii-Der Ida; Bis, Joshua C; Rice, Kenneth M; Sitlani, Colleen M; Kors, Jan A; Xie, Zhijun; Wen, Chengping; Magnani, Jared W; Nelson, Christopher P; Kanters, Jørgen K.; Sinner, Moritz F; Strauch, Konstantin; Peters, Annette; Waldenberger, Melanie; Meitinger, Thomas; Bork-Jensen, Jette; Pedersen, Oluf; Linneberg, Allan; Rudan, Igor; de Boer, Rudolf A; van der Meer, Peter; Yao, Jie; Guo, Xiuqing; Taylor, Kent D; Sotoodehnia, Nona; Rotter, Jerome I; Mook-Kanamori, Dennis O; Trompet, Stella; Rivadeneira, Fernando; Uitterlinden, André; Eijgelsheim, Mark; Padmanabhan, Sandosh; Smith, Blair H; Völzke, Henry; Felix, Stephan B; Homuth, Georg; Völker, Uwe; Mangino, Massimo; Spector, Timothy D; Bots, Michiel L; Perez, Marco; Kähönen, Mika; Raitakari, Olli T; Gudnason, Vilmundur; Arking, Dan E; Munroe, Patricia B; Psaty, Bruce M; van Duijn, Cornelia M; Benjamin, Emelia J; Rosand, Jonathan; Samani, Nilesh J; Hansen, Torben; Kääb, Stefan; Polasek, Ozren; van der Harst, Pim; Heckbert, Susan R; Jukema, J Wouter; Stricker, Bruno H; Hayward, Caroline; Dörr, Marcus; Jamshidi, Yalda; Asselbergs, Folkert W; Kooperberg, Charles; Lehtimäki, Terho; Wilson, James G; Ellinor, Patrick T; Lubitz, Steven A; Isaacs, Aaron.
In:
Circulation. Genomic and precision medicine, Vol. 11, No. 5, e002037, 2018, p. 1-11.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Lin, H, van Setten, J, Smith, AV, Bihlmeyer, NA, Warren, HR, Brody, JA, Radmanesh, F, Hall, L, Grarup, N, Müller-Nurasyid, M, Boutin, T, Verweij, N, Lin, HJ, Li-Gao, R, van den Berg, ME, Marten, J, Weiss, S, Prins, BP, Haessler, J, Lyytikäinen, L-P, Mei, H, Harris, TB, Launer, LJ, Li, M, Alonso, A, Soliman, EZ, Connell, JM, Huang, PL, Weng, L-C, Jameson, HS, Hucker, W, Hanley, A, Tucker, NR, Chen, Y-DI, Bis, JC, Rice, KM, Sitlani, CM, Kors, JA, Xie, Z, Wen, C, Magnani, JW, Nelson, CP
, Kanters, JK, Sinner, MF, Strauch, K, Peters, A, Waldenberger, M, Meitinger, T, Bork-Jensen, J
, Pedersen, O, Linneberg, A, Rudan, I, de Boer, RA, van der Meer, P, Yao, J, Guo, X, Taylor, KD, Sotoodehnia, N, Rotter, JI, Mook-Kanamori, DO, Trompet, S, Rivadeneira, F, Uitterlinden, A, Eijgelsheim, M, Padmanabhan, S, Smith, BH, Völzke, H, Felix, SB, Homuth, G, Völker, U, Mangino, M, Spector, TD, Bots, ML, Perez, M, Kähönen, M, Raitakari, OT, Gudnason, V, Arking, DE, Munroe, PB, Psaty, BM, van Duijn, CM, Benjamin, EJ, Rosand, J, Samani, NJ
, Hansen, T, Kääb, S, Polasek, O, van der Harst, P, Heckbert, SR, Jukema, JW, Stricker, BH, Hayward, C, Dörr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimäki, T, Wilson, JG, Ellinor, PT, Lubitz, SA & Isaacs, A 2018, '
Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval',
Circulation. Genomic and precision medicine, vol. 11, no. 5, e002037, pp. 1-11.
https://doi.org/10.1161/CIRCGEN.117.002037
APA
Lin, H., van Setten, J., Smith, A. V., Bihlmeyer, N. A., Warren, H. R., Brody, J. A., Radmanesh, F., Hall, L., Grarup, N., Müller-Nurasyid, M., Boutin, T., Verweij, N., Lin, H. J., Li-Gao, R., van den Berg, M. E., Marten, J., Weiss, S., Prins, B. P., Haessler, J., ... Isaacs, A. (2018).
Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.
Circulation. Genomic and precision medicine,
11(5), 1-11. [e002037].
https://doi.org/10.1161/CIRCGEN.117.002037
Vancouver
Lin H, van Setten J, Smith AV, Bihlmeyer NA, Warren HR, Brody JA et al.
Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.
Circulation. Genomic and precision medicine. 2018;11(5):1-11. e002037.
https://doi.org/10.1161/CIRCGEN.117.002037
Author
Lin, Honghuang ; van Setten, Jessica ; Smith, Albert V ; Bihlmeyer, Nathan A ; Warren, Helen R ; Brody, Jennifer A ; Radmanesh, Farid ; Hall, Leanne ; Grarup, Niels ; Müller-Nurasyid, Martina ; Boutin, Thibaud ; Verweij, Niek ; Lin, Henry J ; Li-Gao, Ruifang ; van den Berg, Marten E ; Marten, Jonathan ; Weiss, Stefan ; Prins, Bram P ; Haessler, Jeffrey ; Lyytikäinen, Leo-Pekka ; Mei, Hao ; Harris, Tamara B ; Launer, Lenore J ; Li, Man ; Alonso, Alvaro ; Soliman, Elsayed Z ; Connell, John M ; Huang, Paul L ; Weng, Lu-Chen ; Jameson, Heather S ; Hucker, William ; Hanley, Alan ; Tucker, Nathan R ; Chen, Yii-Der Ida ; Bis, Joshua C ; Rice, Kenneth M ; Sitlani, Colleen M ; Kors, Jan A ; Xie, Zhijun ; Wen, Chengping ; Magnani, Jared W ; Nelson, Christopher P ; Kanters, Jørgen K. ; Sinner, Moritz F ; Strauch, Konstantin ; Peters, Annette ; Waldenberger, Melanie ; Meitinger, Thomas ; Bork-Jensen, Jette ; Pedersen, Oluf ; Linneberg, Allan ; Rudan, Igor ; de Boer, Rudolf A ; van der Meer, Peter ; Yao, Jie ; Guo, Xiuqing ; Taylor, Kent D ; Sotoodehnia, Nona ; Rotter, Jerome I ; Mook-Kanamori, Dennis O ; Trompet, Stella ; Rivadeneira, Fernando ; Uitterlinden, André ; Eijgelsheim, Mark ; Padmanabhan, Sandosh ; Smith, Blair H ; Völzke, Henry ; Felix, Stephan B ; Homuth, Georg ; Völker, Uwe ; Mangino, Massimo ; Spector, Timothy D ; Bots, Michiel L ; Perez, Marco ; Kähönen, Mika ; Raitakari, Olli T ; Gudnason, Vilmundur ; Arking, Dan E ; Munroe, Patricia B ; Psaty, Bruce M ; van Duijn, Cornelia M ; Benjamin, Emelia J ; Rosand, Jonathan ; Samani, Nilesh J ; Hansen, Torben ; Kääb, Stefan ; Polasek, Ozren ; van der Harst, Pim ; Heckbert, Susan R ; Jukema, J Wouter ; Stricker, Bruno H ; Hayward, Caroline ; Dörr, Marcus ; Jamshidi, Yalda ; Asselbergs, Folkert W ; Kooperberg, Charles ; Lehtimäki, Terho ; Wilson, James G ; Ellinor, Patrick T ; Lubitz, Steven A ; Isaacs, Aaron. / Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval. In: Circulation. Genomic and precision medicine. 2018 ; Vol. 11, No. 5. pp. 1-11.
Bibtex
@article{f5faa796914d4b2db1c6b39b022ae71b,
title = "Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval",
abstract = "BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval.RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus.CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.",
author = "Honghuang Lin and {van Setten}, Jessica and Smith, {Albert V} and Bihlmeyer, {Nathan A} and Warren, {Helen R} and Brody, {Jennifer A} and Farid Radmanesh and Leanne Hall and Niels Grarup and Martina M{\"u}ller-Nurasyid and Thibaud Boutin and Niek Verweij and Lin, {Henry J} and Ruifang Li-Gao and {van den Berg}, {Marten E} and Jonathan Marten and Stefan Weiss and Prins, {Bram P} and Jeffrey Haessler and Leo-Pekka Lyytik{\"a}inen and Hao Mei and Harris, {Tamara B} and Launer, {Lenore J} and Man Li and Alvaro Alonso and Soliman, {Elsayed Z} and Connell, {John M} and Huang, {Paul L} and Lu-Chen Weng and Jameson, {Heather S} and William Hucker and Alan Hanley and Tucker, {Nathan R} and Chen, {Yii-Der Ida} and Bis, {Joshua C} and Rice, {Kenneth M} and Sitlani, {Colleen M} and Kors, {Jan A} and Zhijun Xie and Chengping Wen and Magnani, {Jared W} and Nelson, {Christopher P} and Kanters, {J{\o}rgen K.} and Sinner, {Moritz F} and Konstantin Strauch and Annette Peters and Melanie Waldenberger and Thomas Meitinger and Jette Bork-Jensen and Oluf Pedersen and Allan Linneberg and Igor Rudan and {de Boer}, {Rudolf A} and {van der Meer}, Peter and Jie Yao and Xiuqing Guo and Taylor, {Kent D} and Nona Sotoodehnia and Rotter, {Jerome I} and Mook-Kanamori, {Dennis O} and Stella Trompet and Fernando Rivadeneira and Andr{\'e} Uitterlinden and Mark Eijgelsheim and Sandosh Padmanabhan and Smith, {Blair H} and Henry V{\"o}lzke and Felix, {Stephan B} and Georg Homuth and Uwe V{\"o}lker and Massimo Mangino and Spector, {Timothy D} and Bots, {Michiel L} and Marco Perez and Mika K{\"a}h{\"o}nen and Raitakari, {Olli T} and Vilmundur Gudnason and Arking, {Dan E} and Munroe, {Patricia B} and Psaty, {Bruce M} and {van Duijn}, {Cornelia M} and Benjamin, {Emelia J} and Jonathan Rosand and Samani, {Nilesh J} and Torben Hansen and Stefan K{\"a}{\"a}b and Ozren Polasek and {van der Harst}, Pim and Heckbert, {Susan R} and Jukema, {J Wouter} and Stricker, {Bruno H} and Caroline Hayward and Marcus D{\"o}rr and Yalda Jamshidi and Asselbergs, {Folkert W} and Charles Kooperberg and Terho Lehtim{\"a}ki and Wilson, {James G} and Ellinor, {Patrick T} and Lubitz, {Steven A} and Aaron Isaacs",
note = "{\textcopyright} 2018 American Heart Association, Inc.",
year = "2018",
doi = "10.1161/CIRCGEN.117.002037",
language = "English",
volume = "11",
pages = "1--11",
journal = "Circulation. Genomic and precision medicine",
issn = "2574-8300",
publisher = "American Heart Association",
number = "5",
}
RIS
TY - JOUR
T1 - Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval
AU - Lin, Honghuang
AU - van Setten, Jessica
AU - Smith, Albert V
AU - Bihlmeyer, Nathan A
AU - Warren, Helen R
AU - Brody, Jennifer A
AU - Radmanesh, Farid
AU - Hall, Leanne
AU - Grarup, Niels
AU - Müller-Nurasyid, Martina
AU - Boutin, Thibaud
AU - Verweij, Niek
AU - Lin, Henry J
AU - Li-Gao, Ruifang
AU - van den Berg, Marten E
AU - Marten, Jonathan
AU - Weiss, Stefan
AU - Prins, Bram P
AU - Haessler, Jeffrey
AU - Lyytikäinen, Leo-Pekka
AU - Mei, Hao
AU - Harris, Tamara B
AU - Launer, Lenore J
AU - Li, Man
AU - Alonso, Alvaro
AU - Soliman, Elsayed Z
AU - Connell, John M
AU - Huang, Paul L
AU - Weng, Lu-Chen
AU - Jameson, Heather S
AU - Hucker, William
AU - Hanley, Alan
AU - Tucker, Nathan R
AU - Chen, Yii-Der Ida
AU - Bis, Joshua C
AU - Rice, Kenneth M
AU - Sitlani, Colleen M
AU - Kors, Jan A
AU - Xie, Zhijun
AU - Wen, Chengping
AU - Magnani, Jared W
AU - Nelson, Christopher P
AU - Kanters, Jørgen K.
AU - Sinner, Moritz F
AU - Strauch, Konstantin
AU - Peters, Annette
AU - Waldenberger, Melanie
AU - Meitinger, Thomas
AU - Bork-Jensen, Jette
AU - Pedersen, Oluf
AU - Linneberg, Allan
AU - Rudan, Igor
AU - de Boer, Rudolf A
AU - van der Meer, Peter
AU - Yao, Jie
AU - Guo, Xiuqing
AU - Taylor, Kent D
AU - Sotoodehnia, Nona
AU - Rotter, Jerome I
AU - Mook-Kanamori, Dennis O
AU - Trompet, Stella
AU - Rivadeneira, Fernando
AU - Uitterlinden, André
AU - Eijgelsheim, Mark
AU - Padmanabhan, Sandosh
AU - Smith, Blair H
AU - Völzke, Henry
AU - Felix, Stephan B
AU - Homuth, Georg
AU - Völker, Uwe
AU - Mangino, Massimo
AU - Spector, Timothy D
AU - Bots, Michiel L
AU - Perez, Marco
AU - Kähönen, Mika
AU - Raitakari, Olli T
AU - Gudnason, Vilmundur
AU - Arking, Dan E
AU - Munroe, Patricia B
AU - Psaty, Bruce M
AU - van Duijn, Cornelia M
AU - Benjamin, Emelia J
AU - Rosand, Jonathan
AU - Samani, Nilesh J
AU - Hansen, Torben
AU - Kääb, Stefan
AU - Polasek, Ozren
AU - van der Harst, Pim
AU - Heckbert, Susan R
AU - Jukema, J Wouter
AU - Stricker, Bruno H
AU - Hayward, Caroline
AU - Dörr, Marcus
AU - Jamshidi, Yalda
AU - Asselbergs, Folkert W
AU - Kooperberg, Charles
AU - Lehtimäki, Terho
AU - Wilson, James G
AU - Ellinor, Patrick T
AU - Lubitz, Steven A
AU - Isaacs, Aaron
N1 - © 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval.RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus.CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.
AB - BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval.RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus.CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.
U2 - 10.1161/CIRCGEN.117.002037
DO - 10.1161/CIRCGEN.117.002037
M3 - Journal article
C2 - 29748316
VL - 11
SP - 1
EP - 11
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 2574-8300
IS - 5
M1 - e002037
ER -