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

GF Mitchell; Germaine Verwoert; KV Tarasov; Aaron Isaacs; AV Smith; null Yasmin; ER Rietzschel; T Tanaka; YM Liu; A Parsa; SS Najjar; KM O'Shaughnessy; S Sigurdsson; ML De Buyzere; MG Larson; MPS Sie; JS Andrews; WS Post; F.U.S. Mattace Raso; CM McEniery; G Eiriksdottir; P Segers; RS Vasan; MJE van Rijn; TD Howard; PF McArdle; Abbas Dehghan; ES Jewell; SJ Newhouse; S Bekaert; NM Hamburg; AB Newman; Bert Hofman; A Scuteri; D De Bacquer; Arfan Ikram; BM Psaty; C Fuchsberger; M Olden; LV Wain; P Elliott; NL Smith; Janine Felix; J Erdmann; JA Vita; K Sutton-Tyrrell; E.J.G. Sijbrands; S Sanna; LJ (Lenore) Launer; T Meyer; AD Johnson; Anna Schut; DM Herrington; Fernando Rivadeneira; M Uda; IB Wilkinson; T Aspelund; TC Gillebert; L Van Bortel; EJ Benjamin; Ben Oostra; JZ (Jing Zhong) Ding; Q Gibson; André Uitterlinden; GR Abecasis; JR Cockcroft; V Gudnason; GG De Backer; L Ferrucci; TB Harris; AR Shuldiner; Cornelia Duijn; D Levy; EG Lakatta; JCM Witteman

doi:10.1161/CIRCGENETICS.111.959817

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

GF Mitchell, Germaine Verwoert, KV Tarasov, Aaron Isaacs, AV Smith, Yasmin, ER Rietzschel, T Tanaka, YM Liu, A Parsa, SS Najjar, KM O'Shaughnessy, S Sigurdsson, ML De Buyzere, MG Larson, MPS Sie, JS Andrews, WS Post, F.U.S. Mattace Raso, CM McEnieryG Eiriksdottir, P Segers, RS Vasan, MJE van Rijn, TD Howard, PF McArdle, Abbas Dehghan, ES Jewell, SJ Newhouse, S Bekaert, NM Hamburg, AB Newman, Bert Hofman, A Scuteri, D De Bacquer, Arfan Ikram, BM Psaty, C Fuchsberger, M Olden, LV Wain, P Elliott, NL Smith, Janine Felix, J Erdmann, JA Vita, K Sutton-Tyrrell, E.J.G. Sijbrands, S Sanna, LJ (Lenore) Launer, T Meyer, AD Johnson, Anna Schut, DM Herrington, Fernando Rivadeneira, M Uda, IB Wilkinson, T Aspelund, TC Gillebert, L Van Bortel, EJ Benjamin, Ben Oostra, JZ (Jing Zhong) Ding, Q Gibson, André Uitterlinden, GR Abecasis, JR Cockcroft, V Gudnason, GG De Backer, L Ferrucci, TB Harris, AR Shuldiner, Cornelia Duijn, D Levy, EG Lakatta, JCM Witteman

Research output: Contribution to journal › Article › Academic

83 Citations (Scopus)

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); replicati 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. (Circ Cardiovasc Genet. 2012;5:81-90.)

Original language	Undefined/Unknown
Pages (from-to)	81-90
Number of pages	10
Journal	Circulation-cardiovascular genetics
Volume	5
Issue number	1
DOIs	https://doi.org/10.1161/CIRCGENETICS.111.959817
Publication status	Published - 2012

Research programs

EMC COEUR-09
EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC OR-01-39-08

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/CIRCGENETICS.111.959817

http://hdl.handle.net/1765/70790

Cite this

Mitchell, GF., Verwoert, G., Tarasov, KV., Isaacs, A., Smith, AV., Yasmin, Rietzschel, ER., Tanaka, T., Liu, YM., Parsa, A., Najjar, SS., O'Shaughnessy, KM., Sigurdsson, S., De Buyzere, ML., Larson, MG., Sie, MPS., Andrews, JS., Post, WS., Mattace Raso, F. U. S., ... Witteman, JCM. (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. https://doi.org/10.1161/CIRCGENETICS.111.959817

@article{dd90221ed2ec4d5fa45823a9c00c29be,

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",

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); replicati 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. (Circ Cardiovasc Genet. 2012;5:81-90.)",

author = "GF Mitchell and Germaine Verwoert and KV Tarasov and Aaron Isaacs and AV Smith and Yasmin and ER Rietzschel and T Tanaka and YM Liu and A Parsa and SS Najjar and KM O'Shaughnessy and S Sigurdsson and {De Buyzere}, ML and MG Larson and MPS Sie and JS Andrews and WS Post and {Mattace Raso}, F.U.S. and CM McEniery and G Eiriksdottir and P Segers and RS Vasan and {van Rijn}, MJE and TD Howard and PF McArdle and Abbas Dehghan and ES Jewell and SJ Newhouse and S Bekaert and NM Hamburg and AB Newman and Bert Hofman and A Scuteri and {De Bacquer}, D and Arfan Ikram and BM Psaty and C Fuchsberger and M Olden and LV Wain and P Elliott and NL Smith and Janine Felix and J Erdmann and JA Vita and K Sutton-Tyrrell and E.J.G. Sijbrands and S Sanna and Launer, {LJ (Lenore)} and T Meyer and AD Johnson and Anna Schut and DM Herrington and Fernando Rivadeneira and M Uda and IB Wilkinson and T Aspelund and TC Gillebert and {Van Bortel}, L and EJ Benjamin and Ben Oostra and Ding, {JZ (Jing Zhong)} and Q Gibson and Andr{\'e} Uitterlinden and GR Abecasis and JR Cockcroft and V Gudnason and {De Backer}, GG and L Ferrucci and TB Harris and AR Shuldiner and Cornelia Duijn and D Levy and EG Lakatta and JCM Witteman",

year = "2012",

doi = "10.1161/CIRCGENETICS.111.959817",

language = "Undefined/Unknown",

volume = "5",

pages = "81--90",

journal = "Circulation-cardiovascular genetics",

issn = "1942-325X",

publisher = "Lippincott Williams & Wilkins",

number = "1",

}

Mitchell, GF, Verwoert, G, Tarasov, KV, Isaacs, A, Smith, AV, Yasmin, Rietzschel, ER, Tanaka, T, Liu, YM, Parsa, A, Najjar, SS, O'Shaughnessy, KM, Sigurdsson, S, De Buyzere, ML, Larson, MG, Sie, MPS, Andrews, JS, Post, WS, Mattace Raso, FUS, McEniery, CM, Eiriksdottir, G, Segers, P, Vasan, RS, van Rijn, MJE, Howard, TD, McArdle, PF, Dehghan, A, Jewell, ES, Newhouse, SJ, Bekaert, S, Hamburg, NM, Newman, AB, Hofman, B, Scuteri, A, De Bacquer, D, Ikram, A, Psaty, BM, Fuchsberger, C, Olden, M, Wain, LV, Elliott, P, Smith, NL, Felix, J, Erdmann, J, Vita, JA, Sutton-Tyrrell, K, Sijbrands, EJG, Sanna, S, Launer, LJ, Meyer, T, Johnson, AD, Schut, A, Herrington, DM, Rivadeneira, F, Uda, M, Wilkinson, IB, Aspelund, T, Gillebert, TC, Van Bortel, L, Benjamin, EJ, Oostra, B, Ding, JZ, Gibson, Q, Uitterlinden, A, Abecasis, GR, Cockcroft, JR, Gudnason, V, De Backer, GG, Ferrucci, L, Harris, TB, Shuldiner, AR, Duijn, C, Levy, D, Lakatta, EG & Witteman, JCM 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, vol. 5, no. 1, pp. 81-90. https://doi.org/10.1161/CIRCGENETICS.111.959817

TY - JOUR

T1 - 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

AU - Mitchell, GF

AU - Verwoert, Germaine

AU - Tarasov, KV

AU - Isaacs, Aaron

AU - Smith, AV

AU - Yasmin, null

AU - Rietzschel, ER

AU - Tanaka, T

AU - Liu, YM

AU - Parsa, A

AU - Najjar, SS

AU - O'Shaughnessy, KM

AU - Sigurdsson, S

AU - De Buyzere, ML

AU - Larson, MG

AU - Sie, MPS

AU - Andrews, JS

AU - Post, WS

AU - Mattace Raso, F.U.S.

AU - McEniery, CM

AU - Eiriksdottir, G

AU - Segers, P

AU - Vasan, RS

AU - van Rijn, MJE

AU - Howard, TD

AU - McArdle, PF

AU - Dehghan, Abbas

AU - Jewell, ES

AU - Newhouse, SJ

AU - Bekaert, S

AU - Hamburg, NM

AU - Newman, AB

AU - Hofman, Bert

AU - Scuteri, A

AU - De Bacquer, D

AU - Ikram, Arfan

AU - Psaty, BM

AU - Fuchsberger, C

AU - Olden, M

AU - Wain, LV

AU - Elliott, P

AU - Smith, NL

AU - Felix, Janine

AU - Erdmann, J

AU - Vita, JA

AU - Sutton-Tyrrell, K

AU - Sijbrands, E.J.G.

AU - Sanna, S

AU - Launer, LJ (Lenore)

AU - Meyer, T

AU - Johnson, AD

AU - Schut, Anna

AU - Herrington, DM

AU - Rivadeneira, Fernando

AU - Uda, M

AU - Wilkinson, IB

AU - Aspelund, T

AU - Gillebert, TC

AU - Van Bortel, L

AU - Benjamin, EJ

AU - Oostra, Ben

AU - Ding, JZ (Jing Zhong)

AU - Gibson, Q

AU - Uitterlinden, André

AU - Abecasis, GR

AU - Cockcroft, JR

AU - Gudnason, V

AU - De Backer, GG

AU - Ferrucci, L

AU - Harris, TB

AU - Shuldiner, AR

AU - Duijn, Cornelia

AU - Levy, D

AU - Lakatta, EG

AU - Witteman, JCM

PY - 2012

Y1 - 2012

N2 - 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); replicati 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. (Circ Cardiovasc Genet. 2012;5:81-90.)

AB - 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); replicati 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. (Circ Cardiovasc Genet. 2012;5:81-90.)

U2 - 10.1161/CIRCGENETICS.111.959817

DO - 10.1161/CIRCGENETICS.111.959817

M3 - Article

C2 - 22068335

SN - 1942-325X

VL - 5

SP - 81

EP - 90

JO - Circulation-cardiovascular genetics

JF - Circulation-cardiovascular genetics

IS - 1

ER -