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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 and Donnelly, Louise A, et al. (2014) In Nature Communications 5.
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.
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Nature Communications
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5
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Nature Publishing Group
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  • pmid:25350695
  • wos:000343977100003
  • scopus:84919752308
ISSN
2041-1723
DOI
10.1038/ncomms6068
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English
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d95a45f6-c850-43c3-8ecc-22aceb449b61 (old id 4733012)
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http://www.ncbi.nlm.nih.gov/pubmed/25350695?dopt=Abstract
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2014-11-10 19:44:50
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@article{d95a45f6-c850-43c3-8ecc-22aceb449b61,
  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.},
  articleno    = {5068},
  author       = {Postmus, Iris and Trompet, Stella and Deshmukh, Harshal A and Barnes, Michael R and Li, Xiaohui and Warren, Helen R and Chasman, Daniel I and Zhou, Kaixin and Arsenault, Benoit J and Donnelly, Louise A and Wiggins, Kerri L and Avery, Christy L and Griffin, Paula and Feng, QiPing and Taylor, Kent D and Li, Guo and Evans, Daniel S and Smith, Albert V and de Keyser, Catherine E and Johnson, Andrew D and de Craen, Anton J M and Stott, David J and Buckley, Brendan M and Ford, Ian and Westendorp, Rudi G J and Eline Slagboom, P and Sattar, Naveed and Munroe, Patricia B and Sever, Peter and Poulter, Neil and Stanton, Alice and Shields, Denis C and O'Brien, Eoin and Shaw-Hawkins, Sue and Ida Chen, Y-D and Nickerson, Deborah A and Smith, Joshua D and Pierre Dubé, Marie and Matthijs Boekholdt, S and Kees Hovingh, G and Kastelein, John J P and McKeigue, Paul M and Betteridge, John and Neil, Andrew and Durrington, Paul N and Doney, Alex and Carr, Fiona and Morris, Andrew and McCarthy, Mark I and Groop, Leif and Ahlqvist, Emma and Bis, Joshua C and Rice, Kenneth and Smith, Nicholas L and Lumley, Thomas and Whitsel, Eric A and Stürmer, Til and Boerwinkle, Eric and Ngwa, Julius S and O'Donnell, Christopher J and Vasan, Ramachandran S and Wei, Wei-Qi and Wilke, Russell A and Liu, Ching-Ti and Sun, Fangui and Guo, Xiuqing and Heckbert, Susan R and Post, Wendy and Sotoodehnia, Nona and Arnold, Alice M and Stafford, Jeanette M and Ding, Jingzhong and Herrington, David M and Kritchevsky, Stephen B and Eiriksdottir, Gudny and Launer, Leonore J and Harris, Tamara B and Chu, Audrey Y and Giulianini, Franco and MacFadyen, Jean G and Barratt, Bryan J and Nyberg, Fredrik and Stricker, Bruno H and Uitterlinden, André G and Hofman, Albert and Rivadeneira, Fernando and Emilsson, Valur and Franco, Oscar H and Ridker, Paul M and Gudnason, Vilmundur and Liu, Yongmei and Denny, Joshua C and Ballantyne, Christie M and Rotter, Jerome I and Adrienne Cupples, L and Psaty, Bruce M and Palmer, Colin N A and Tardif, Jean-Claude and Colhoun, Helen M and Hitman, Graham and Krauss, Ronald M and Wouter Jukema, J and Caulfield, Mark J},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.},
  url          = {http://dx.doi.org/10.1038/ncomms6068},
  volume       = {5},
  year         = {2014},
}