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Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium

Gary F Mitchell, Germaine C Verwoert, Kirill V Tarasov, Aaron Isaacs, Albert V Smith, . Yasmin, Ernst Rietzschel UGent, Toshiko Tanaka, Yongmei Liu and Afshin Parsa, et al. (2012) CIRCULATION-CARDIOVASCULAR GENETICS. 5(1). p.81-90
abstract
BACKGROUND: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, beta=-0.075+/-0.012 SD/allele, P=2.8x10(-10); replication beta=-0.086+/-0.020 SD/allele, P=1.4x10(-6)). Combined results for rs7152623 from 11 cohorts gave beta=-0.076+/-0.010 SD/allele, P=3.1x10(-15). The association persisted when adjusted for mean arterial pressure (beta=-0.060+/-0.009 SD/allele, P=1.0x10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, beta=-0.081+/-0.014 SD/allele, P=2.3x10(-9)) and older (9 cohorts, n=12 026, beta=-0.061+/-0.014 SD/allele, P=9.4x10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). CONCLUSIONS: Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
journal title
CIRCULATION-CARDIOVASCULAR GENETICS
Circ.-Cardiovasc. Genet.
volume
5
issue
1
pages
81 - 90
Web of Science type
Article
Web of Science id
000309884100015
JCR category
CARDIAC & CARDIOVASCULAR SYSTEMS
JCR impact factor
6.728 (2012)
JCR rank
6/120 (2012)
JCR quartile
1 (2012)
ISSN
1942-325X
DOI
10.1161/CIRCGENETICS.111.959817
project
The Asklepios project
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2107434
handle
http://hdl.handle.net/1854/LU-2107434
date created
2012-05-15 17:21:05
date last changed
2015-06-17 10:02:38
@article{2107434,
  abstract     = {BACKGROUND: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events.
METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, beta=-0.075+/-0.012 SD/allele, P=2.8x10(-10); replication beta=-0.086+/-0.020 SD/allele, P=1.4x10(-6)). Combined results for rs7152623 from 11 cohorts gave beta=-0.076+/-0.010 SD/allele, P=3.1x10(-15). The association persisted when adjusted for mean arterial pressure (beta=-0.060+/-0.009 SD/allele, P=1.0x10(-11)). Results were consistent in younger ({\textlangle}55 years, 6 cohorts, n=13 914, beta=-0.081+/-0.014 SD/allele, P=2.3x10(-9)) and older (9 cohorts, n=12 026, beta=-0.061+/-0.014 SD/allele, P=9.4x10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004).
CONCLUSIONS: Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.},
  author       = {Mitchell, Gary F and Verwoert, Germaine C and Tarasov, Kirill V and Isaacs, Aaron and Smith, Albert V and Yasmin, . and Rietzschel, Ernst and Tanaka, Toshiko and Liu, Yongmei and Parsa, Afshin and Najjar, Samer S and O'Shaughnessy, Kevin M and Sigurdsson, Sigurdur and De Buyzere, Marc and Larson, Martin G and Sie, Mark PS and Andrews, Jeanette S and Post, Wendy S and Mattace-Raso, Francesco US and McEniery, Carmel M and Eiriksdottir, Gudny and Segers, Patrick and Vasan, Ramachandran S and van Rijn, Marie Josee E and Howard, Timothy D and McArdle, Patrick F and Dehghan, Abbas and Jewell, Elizabeth S and Newhouse, Stephen J and Bekaert, Sofie and Hamburg, Naomi M and Newman, Anne B and Hofman, Albert and Scuteri, Angelo and De Bacquer, Dirk and Arfan Ikram, Mohammad and Psaty, Bruce M and Fuchsberger, Christian and Olden, Mathhias and Wain, Louise V and Elliott, Paul and Smith, Nicholas L and Felix, Janine F and Erdmann, Jeanette and Vita, Joseph A and Sutton-Tyrrell, Kim and Sijbrands, Eric JG and Sanna, Serena and Launer, Lenore J and De Meyer, Tim and Johnson, Andrew D and Schut, Anna FC and Herrington, David M and Rivadeneira, Fernando and Uda, Manuela and Wilkinson, Ian B and Aspelund, Thor and Gillebert, Thierry and Van Bortel, Lucas and Benjamin, Emelia J and Oostra, Ben A and Ding, Jingzhong and Gibson, Quince and Uitterlinden, Andr{\'e} G and Abecasis, Gon\c{c}alo R and Cockcroft, John R and Gudnason, Vilmundur and De Backer, Gui and Ferrucci, Luigi and Harris, Tamara B and Shuldiner, Alan R and van Duijn, Cornelia M and Levy, Daniel and Lakatta, Edward G and Witteman, Jacqueline CM},
  issn         = {1942-325X},
  journal      = {CIRCULATION-CARDIOVASCULAR GENETICS},
  language     = {eng},
  number       = {1},
  pages        = {81--90},
  title        = {Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium},
  url          = {http://dx.doi.org/10.1161/CIRCGENETICS.111.959817},
  volume       = {5},
  year         = {2012},
}

Chicago
Mitchell, Gary F, Germaine C Verwoert, Kirill V Tarasov, Aaron Isaacs, Albert V Smith, . Yasmin, Ernst Rietzschel, et al. 2012. “Common Genetic Variation in the 3’-BCL11B Gene Desert Is Associated with Carotid-femoral Pulse Wave Velocity and Excess Cardiovascular Disease Risk: The AortaGen Consortium.” Circulation-cardiovascular Genetics 5 (1): 81–90.
APA
Mitchell, G. F., Verwoert, G. C., Tarasov, K. V., Isaacs, A., Smith, A. V., Yasmin, ., Rietzschel, E., et al. (2012). Common genetic variation in the 3’-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. CIRCULATION-CARDIOVASCULAR GENETICS, 5(1), 81–90.
Vancouver
1.
Mitchell GF, Verwoert GC, Tarasov KV, Isaacs A, Smith AV, Yasmin ., et al. Common genetic variation in the 3’-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. CIRCULATION-CARDIOVASCULAR GENETICS. 2012;5(1):81–90.
MLA
Mitchell, Gary F, Germaine C Verwoert, Kirill V Tarasov, et al. “Common Genetic Variation in the 3’-BCL11B Gene Desert Is Associated with Carotid-femoral Pulse Wave Velocity and Excess Cardiovascular Disease Risk: The AortaGen Consortium.” CIRCULATION-CARDIOVASCULAR GENETICS 5.1 (2012): 81–90. Print.