Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Postmus, Iris, Trompet, Stella, Deshmukh, Harshal A., Barnes, Michael R., Li, Xiaohui, Warren, Helen R., Chasman, Daniel I., Zhou, Kaixin, Arsenault, Benoit J., Donnelly, Louise A., Wiggins, Kerri L., Avery, Christy L., Griffin, Paula, Feng, QiPing, Taylor, Kent D., Li, Guo, Evans, Daniel S., Smith, Albert V., De Keyser, Catherine E., Johnson, Andrew D., De Craen, Anton J. M., Stott, David J., Buckley, Brendan M., Ford, Ian, Westendorp, Rudi G. J., Slagboom, P. Eline, Sattar, Naveed, Munroe, Patricia B., Sever, Peter, Poulter, Neil, Stanton, Alice, Shields, Denis C., O'Brien, Eoin, Shaw-Hawkins, Sue, Ida Chen, Y. -D., Nickerson, Deborah A., Smith, Joshua D., Dube, Marie Pierre, Boekholdt, S. Matthijs, Hovingh, G. Kees, Kastelein, John J. P., McKeigue, Paul M., Betteridge, John, Neil, Andrew, Durrington, Paul N., Doney, Alex, Carr, Fiona, Morris, Andrew, McCarthy, Mark I., Groop, Leif, Ahlqvist, Emma, Barroso, Ines, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Spencer, Chris C. A., Band, Gavin, Bellenguez, Celine, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Donnelly, Peter, Langford, Cordelia, Hunt, Sarah E., Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J., Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T., Liddle, Jennifer, Potter, Simon C., Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Bis, Joshua C., Rice, Kenneth, Smith, Nicholas L., Lumley, Thomas, Whitsel, Eric A., Sturmer, Til, Boerwinkle, Eric, Ngwa, Julius S., O'Donnell, Christopher J., Vasan, Ramachandran S., Wei, Wei-Qi, Wilke, Russell A., Liu, Ching-Ti, Sun, Fangui, Guo, Xiuqing, Heckbert, Susan R., Post, Wendy, Sotoodehnia, Nona, Arnold, Alice M., Stafford, Jeanette M., Ding, Jingzhong, Herrington, David M., Kritchevsky, Stephen B., Eiriksdottir, Gudny, Launer, Leonore J., Harris, Tamara B., Chu, Audrey Y., Giulianini, Franco, MacFadyen, Jean G., Barratt, Bryan J., Nyberg, Fredrik, Stricker, Bruno H., Uitterlinden, Andre G., Hofman, Albert, Rivadeneira, Fernando, Emilsson, Valur, Franco, Oscar H., Ridker, Paul M., Gudnason, Vilmundur, Liu, Yongmei, Denny, Joshua C., Ballantyne, Christie M., Rotter, Jerome I., Cupples, L. Adrienne, Psaty, Bruce M., Tardif, Jean-Claude, Colhoun, Helen M., Hitman, Graham, Krauss, Ronald M., Jukema, J. Wouter and Caulfield, Mark J. (2014) Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nature Communications, 5 . doi:10.1038/ncomms6068


Author Postmus, Iris
Trompet, Stella
Deshmukh, Harshal A.
Barnes, Michael R.
Li, Xiaohui
Warren, Helen R.
Chasman, Daniel I.
Zhou, Kaixin
Arsenault, Benoit J.
Donnelly, Louise A.
Wiggins, Kerri L.
Avery, Christy L.
Griffin, Paula
Feng, QiPing
Taylor, Kent D.
Li, Guo
Evans, Daniel S.
Smith, Albert V.
De Keyser, Catherine E.
Johnson, Andrew D.
De Craen, Anton J. M.
Stott, David J.
Buckley, Brendan M.
Ford, Ian
Westendorp, Rudi G. J.
Slagboom, P. Eline
Sattar, Naveed
Munroe, Patricia B.
Sever, Peter
Poulter, Neil
Stanton, Alice
Shields, Denis C.
O'Brien, Eoin
Shaw-Hawkins, Sue
Ida Chen, Y. -D.
Nickerson, Deborah A.
Smith, Joshua D.
Dube, Marie Pierre
Boekholdt, S. Matthijs
Hovingh, G. Kees
Kastelein, John J. P.
McKeigue, Paul M.
Betteridge, John
Neil, Andrew
Durrington, Paul N.
Doney, Alex
Carr, Fiona
Morris, Andrew
McCarthy, Mark I.
Groop, Leif
Ahlqvist, Emma
Barroso, Ines
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Deloukas, Panos
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S.
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Spencer, Chris C. A.
Band, Gavin
Bellenguez, Celine
Freeman, Colin
Hellenthal, Garrett
Giannoulatou, Eleni
Pirinen, Matti
Pearson, Richard
Strange, Amy
Su, Zhan
Vukcevic, Damjan
Donnelly, Peter
Langford, Cordelia
Hunt, Sarah E.
Edkins, Sarah
Gwilliam, Rhian
Blackburn, Hannah
Bumpstead, Suzannah J.
Dronov, Serge
Gillman, Matthew
Gray, Emma
Hammond, Naomi
Jayakumar, Alagurevathi
McCann, Owen T.
Liddle, Jennifer
Potter, Simon C.
Ravindrarajah, Radhi
Ricketts, Michelle
Waller, Matthew
Weston, Paul
Widaa, Sara
Whittaker, Pamela
Bis, Joshua C.
Rice, Kenneth
Smith, Nicholas L.
Lumley, Thomas
Whitsel, Eric A.
Sturmer, Til
Boerwinkle, Eric
Ngwa, Julius S.
O'Donnell, Christopher J.
Vasan, Ramachandran S.
Wei, Wei-Qi
Wilke, Russell A.
Liu, Ching-Ti
Sun, Fangui
Guo, Xiuqing
Heckbert, Susan R.
Post, Wendy
Sotoodehnia, Nona
Arnold, Alice M.
Stafford, Jeanette M.
Ding, Jingzhong
Herrington, David M.
Kritchevsky, Stephen B.
Eiriksdottir, Gudny
Launer, Leonore J.
Harris, Tamara B.
Chu, Audrey Y.
Giulianini, Franco
MacFadyen, Jean G.
Barratt, Bryan J.
Nyberg, Fredrik
Stricker, Bruno H.
Uitterlinden, Andre G.
Hofman, Albert
Rivadeneira, Fernando
Emilsson, Valur
Franco, Oscar H.
Ridker, Paul M.
Gudnason, Vilmundur
Liu, Yongmei
Denny, Joshua C.
Ballantyne, Christie M.
Rotter, Jerome I.
Cupples, L. Adrienne
Psaty, Bruce M.
Tardif, Jean-Claude
Colhoun, Helen M.
Hitman, Graham
Krauss, Ronald M.
Jukema, J. Wouter
Caulfield, Mark J.
Title Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-10-28
Sub-type Article (original research)
DOI 10.1038/ncomms6068
Open Access Status DOI
Volume 5
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Formatted abstract
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HHSN268200625226C
U01HG004402
U19 HL069757
07/0003525
084727/Z/08/Z
085475/B/08/Z
085475/Z/08/Z
1R01AG032098-01A1
HHSN268200782096C
N01AG62101
N01AG62103
N01AG62106
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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