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 & 4 others Stefan Kääb, Nancy J. Brown, Dan M. Roden, Dawood Darbar

Research output: Contribution to journalArticle

78 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number5
DOIs
StatePublished - Oct 2009

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Coronary Artery Bypass
Atrial Fibrillation
Transplants
Single Nucleotide Polymorphism
Chromosomes
Viverridae
Thoracic Surgery
Odds Ratio
Population

Keywords

  • Arrhythmia
  • Atrial fibrillation
  • Genetics
  • Heart surgery
  • Postoperative complication

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery. / Body, Simon C.; Collard, Charles D.; Shernan, Stanton K.; Fox, Amanda A.; Liu, Kuang Yu; Ritchie, Marylyn D.; Perry, Tjörvi E.; Muehlschlegel, Jochen D.; Aranki, Sary; Donahue, Brian S.; Pretorius, Mias; Estrada, Juan Carlos; Ellinor, Patrick T.; Newton-Cheh, Christopher; Seidman, Christine E.; Seidman, J. G.; Herman, Daniel S.; Lichtner, Peter; Meitinger, Thomas; Pfeufer, Arne; Kääb, Stefan; Brown, Nancy J.; Roden, Dan M.; Darbar, Dawood.

In: Circulation: Cardiovascular Genetics, Vol. 2, No. 5, 10.2009, p. 499-506.

Research output: Contribution to journalArticle

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
Body, Simon C. ; Collard, Charles D. ; Shernan, Stanton K. ; Fox, Amanda A. ; Liu, Kuang Yu ; Ritchie, Marylyn D. ; Perry, Tjörvi E. ; Muehlschlegel, Jochen D. ; Aranki, Sary ; Donahue, Brian S. ; Pretorius, Mias ; Estrada, Juan Carlos ; Ellinor, Patrick T. ; Newton-Cheh, Christopher ; Seidman, Christine E. ; Seidman, J. G. ; Herman, Daniel S. ; Lichtner, Peter ; Meitinger, Thomas ; Pfeufer, Arne ; Kääb, Stefan ; Brown, Nancy J. ; Roden, Dan M. ; Darbar, Dawood. / Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery. In: Circulation: Cardiovascular Genetics. 2009 ; Vol. 2, No. 5. pp. 499-506.
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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

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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.)

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KW - Arrhythmia

KW - Atrial fibrillation

KW - Genetics

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