Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery

Simon C. Body; Charles D. Collard; Stanton K. Shernan; Amanda A. Fox; Kuang Yu Liu; Marylyn D. Ritchie; Tjörvi E. Perry; Jochen D. Muehlschlegel; Sary Aranki; Brian S. Donahue; Mias Pretorius; Juan Carlos Estrada; Patrick T. Ellinor; Christopher Newton-Cheh; Christine E. Seidman; J. G. Seidman; Daniel S. Herman; Peter Lichtner; Thomas Meitinger; Arne Pfeufer; Stefan Kääb; Nancy J. Brown; Dan M. Roden; Dawood Darbar

doi:10.1161/CIRCGENETICS.109.849075

Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery

Simon C. Body, Charles D. Collard, Stanton K. Shernan, Amanda A. Fox, Kuang Yu Liu, Marylyn D. Ritchie, Tjörvi E. Perry, Jochen D. Muehlschlegel, Sary Aranki, Brian S. Donahue, Mias Pretorius, Juan Carlos Estrada, Patrick T. Ellinor, Christopher Newton-Cheh, Christine E. Seidman, J. G. Seidman, Daniel S. Herman, Peter Lichtner, Thomas Meitinger, Arne PfeuferStefan Kääb, Nancy J. Brown, Dan M. Roden, Dawood Darbar

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

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Abstract

Background-Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results-Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0×10^-4 to 3.4×10 ^-6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons. (Circ Cardiovasc Genet. 2009;2:499-506.)

Original language	English (US)
Pages (from-to)	499-506
Number of pages	8
Journal	Circulation: Cardiovascular Genetics
Volume	2
Issue number	5
DOIs	https://doi.org/10.1161/CIRCGENETICS.109.849075
State	Published - Oct 2009

Keywords

Arrhythmia
Atrial fibrillation
Genetics
Heart surgery
Postoperative complication

ASJC Scopus subject areas

Genetics
Cardiology and Cardiovascular Medicine
Genetics(clinical)

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10.1161/CIRCGENETICS.109.849075

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Body, S. C., Collard, C. D., Shernan, S. K., Fox, A. A., Liu, K. Y., Ritchie, M. D., Perry, T. E., Muehlschlegel, J. D., Aranki, S., Donahue, B. S., Pretorius, M., Estrada, J. C., Ellinor, P. T., Newton-Cheh, C., Seidman, C. E., Seidman, J. G., Herman, D. S., Lichtner, P., Meitinger, T., ... Darbar, D. (2009). Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery. Circulation: Cardiovascular Genetics, 2(5), 499-506. https://doi.org/10.1161/CIRCGENETICS.109.849075

Body, SC, Collard, CD, Shernan, SK, Fox, AA, Liu, KY, Ritchie, MD, Perry, TE, Muehlschlegel, JD, Aranki, S, Donahue, BS, Pretorius, M, Estrada, JC, Ellinor, PT, Newton-Cheh, C, Seidman, CE, Seidman, JG, Herman, DS, Lichtner, P, Meitinger, T, Pfeufer, A, Kääb, S, Brown, NJ, Roden, DM & Darbar, D 2009, 'Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery', Circulation: Cardiovascular Genetics, vol. 2, no. 5, pp. 499-506. https://doi.org/10.1161/CIRCGENETICS.109.849075

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title = "Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery",

abstract = "Background-Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results-Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0×10-4 to 3.4×10 -6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons. (Circ Cardiovasc Genet. 2009;2:499-506.)",

keywords = "Arrhythmia, Atrial fibrillation, Genetics, Heart surgery, Postoperative complication",

author = "Body, {Simon C.} and Collard, {Charles D.} and Shernan, {Stanton K.} and Fox, {Amanda A.} and Liu, {Kuang Yu} and Ritchie, {Marylyn D.} and Perry, {Tj{\"o}rvi E.} and Muehlschlegel, {Jochen D.} and Sary Aranki and Donahue, {Brian S.} and Mias Pretorius and Estrada, {Juan Carlos} and Ellinor, {Patrick T.} and Christopher Newton-Cheh and Seidman, {Christine E.} and Seidman, {J. G.} and Herman, {Daniel S.} and Peter Lichtner and Thomas Meitinger and Arne Pfeufer and Stefan K{\"a}{\"a}b and Brown, {Nancy J.} and Roden, {Dan M.} and Dawood Darbar",

year = "2009",

month = oct,

doi = "10.1161/CIRCGENETICS.109.849075",

language = "English (US)",

volume = "2",

pages = "499--506",

journal = "Circulation: Cardiovascular Genetics",

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TY - JOUR

T1 - Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery

AU - Body, Simon C.

AU - Collard, Charles D.

AU - Shernan, Stanton K.

AU - Fox, Amanda A.

AU - Liu, Kuang Yu

AU - Ritchie, Marylyn D.

AU - Perry, Tjörvi E.

AU - Muehlschlegel, Jochen D.

AU - Aranki, Sary

AU - Donahue, Brian S.

AU - Pretorius, Mias

AU - Estrada, Juan Carlos

AU - Ellinor, Patrick T.

AU - Newton-Cheh, Christopher

AU - Seidman, Christine E.

AU - Seidman, J. G.

AU - Herman, Daniel S.

AU - Lichtner, Peter

AU - Meitinger, Thomas

AU - Pfeufer, Arne

AU - Kääb, Stefan

AU - Brown, Nancy J.

AU - Roden, Dan M.

AU - Darbar, Dawood

PY - 2009/10

Y1 - 2009/10

N2 - Background-Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results-Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0×10-4 to 3.4×10 -6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons. (Circ Cardiovasc Genet. 2009;2:499-506.)

AB - Background-Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results-Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0×10-4 to 3.4×10 -6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons. (Circ Cardiovasc Genet. 2009;2:499-506.)

KW - Arrhythmia

KW - Atrial fibrillation

KW - Genetics

KW - Heart surgery

KW - Postoperative complication

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Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery

Abstract

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