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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
- Source :
- Nature Communications; 5, no 5068 (2014), Nature Communications, Nature Communications, 5, Nature Communications, 5. Nature Publishing Group, Nature communications, 5. Nature Publishing Group, Postmus, I, Trompet, S, Deshmukh, H A, Barnes, M R, Li, X, Warren, H R, Chasman, D I, Zhou, K, Arsenault, B J, Donnelly, L A, Wiggins, K L, Avery, C L, Griffin, P, Feng, Q, Taylor, K D, Li, G, Evans, D S, Smith, A V, De Keyser, C E, Johnson, A D, De Craen, A J M, Stott, D J, Buckley, B M, Ford, I, Westendorp, R G J, Eline Slagboom, P, Sattar, N, Munroe, P B, Sever, P, Poulter, N, Stanton, A, Shields, D C, O???brien, E, Shaw-hawkins, S, Ida Chen, Y, Nickerson, D A, Smith, J D, Pierre Dub??, M, Matthijs Boekholdt, S, Kees Hovingh, G, Kastelein, J J P, Mckeigue, P M, Betteridge, J, Neil, A, Durrington, P N, Doney, A, Carr, F, Morris, A, Mccarthy, M I, Groop, L, Ahlqvist, E, Bis, J C, Rice, K, Smith, N L, Lumley, T, Whitsel, E A, St??rmer, T, Boerwinkle, E, Ngwa, J S, O???donnell, C J, Vasan, R S, Wei, W, Wilke, R A, Liu, C, Sun, F, Guo, X, Heckbert, S R, Post, W, Sotoodehnia, N, Arnold, A M, Stafford, J M, Ding, J, Herrington, D M, Kritchevsky, S B, Eiriksdottir, G, Launer, L J, Harris, T B, Chu, A Y, Giulianini, F, Macfadyen, J G, Barratt, B J, Nyberg, F, Stricker, B H, Uitterlinden, A G, Hofman, A, Rivadeneira, F, Emilsson, V, Franco, O H, Ridker, P M, Gudnason, V, Liu, Y, Denny, J C, Ballantyne, C M, Rotter, J I, Adrienne Cupples, L, Psaty, B M, Palmer, C N A, Tardif, J, Colhoun, H M, Hitman, G, Krauss, R M, Wouter Jukema, J, Caulfield, M J, Donnelly, P, Barroso, I, Blackwell, J M, Bramon, E, Brown, M A, Casas, J P, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H S, Mathew, C G, Palmer, C N A, Plomin, R, Rautanen, A, Sawcer, S J, Trembath, R, Viswanathan, A C, Wood, N W, Spencer, C C A, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, Langford, C, Hunt, S E, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, S J, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, O T, Liddle, J, Potter, S C, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, Mathew, C G, Blackwell, J M, Brown, M A, Corvin, A, Mccarthy, M I & Spencer, C C A 2014, ' Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins ', Nature Communications, vol. 5, 5068 . https://doi.org/10.1038/ncomms6068
- Publication Year :
- 2016
- Publisher :
- Springer Nature, 2016.
-
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.<br />Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.
- Subjects :
- Apolipoprotein E
BLOOD
LOCI
General Physics and Astronomy
Genome-wide association study
VARIANTS
030204 cardiovascular system & hematology
Pharmacology
Bioinformatics
THERAPY
DISEASE
chemistry.chemical_compound
0302 clinical medicine
GENE-EXPRESSION
0303 health sciences
Multidisciplinary
biology
3. Good health
Multidisciplinary Sciences
Meta-analysis
WHOLE-GENOME
Science & Technology - Other Topics
lipids (amino acids, peptides, and proteins)
Statin
medicine.drug_class
Endocrinology and Diabetes
Polymorphism, Single Nucleotide
INDUCED MYOPATHY
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Humans
cardiovascular diseases
030304 developmental biology
Genetic association
Science & Technology
Cholesterol
business.industry
HUMAN PREFRONTAL CORTEX
nutritional and metabolic diseases
General Chemistry
Cholesterol, LDL
A300
chemistry
Pharmacogenetics
biology.protein
PLASMA LIPOPROTEIN(A) LEVELS
Hydroxymethylglutaryl-CoA Reductase Inhibitors
SLCO1B1
business
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications; 5, no 5068 (2014), Nature Communications, Nature Communications, 5, Nature Communications, 5. Nature Publishing Group, Nature communications, 5. Nature Publishing Group, Postmus, I, Trompet, S, Deshmukh, H A, Barnes, M R, Li, X, Warren, H R, Chasman, D I, Zhou, K, Arsenault, B J, Donnelly, L A, Wiggins, K L, Avery, C L, Griffin, P, Feng, Q, Taylor, K D, Li, G, Evans, D S, Smith, A V, De Keyser, C E, Johnson, A D, De Craen, A J M, Stott, D J, Buckley, B M, Ford, I, Westendorp, R G J, Eline Slagboom, P, Sattar, N, Munroe, P B, Sever, P, Poulter, N, Stanton, A, Shields, D C, O???brien, E, Shaw-hawkins, S, Ida Chen, Y, Nickerson, D A, Smith, J D, Pierre Dub??, M, Matthijs Boekholdt, S, Kees Hovingh, G, Kastelein, J J P, Mckeigue, P M, Betteridge, J, Neil, A, Durrington, P N, Doney, A, Carr, F, Morris, A, Mccarthy, M I, Groop, L, Ahlqvist, E, Bis, J C, Rice, K, Smith, N L, Lumley, T, Whitsel, E A, St??rmer, T, Boerwinkle, E, Ngwa, J S, O???donnell, C J, Vasan, R S, Wei, W, Wilke, R A, Liu, C, Sun, F, Guo, X, Heckbert, S R, Post, W, Sotoodehnia, N, Arnold, A M, Stafford, J M, Ding, J, Herrington, D M, Kritchevsky, S B, Eiriksdottir, G, Launer, L J, Harris, T B, Chu, A Y, Giulianini, F, Macfadyen, J G, Barratt, B J, Nyberg, F, Stricker, B H, Uitterlinden, A G, Hofman, A, Rivadeneira, F, Emilsson, V, Franco, O H, Ridker, P M, Gudnason, V, Liu, Y, Denny, J C, Ballantyne, C M, Rotter, J I, Adrienne Cupples, L, Psaty, B M, Palmer, C N A, Tardif, J, Colhoun, H M, Hitman, G, Krauss, R M, Wouter Jukema, J, Caulfield, M J, Donnelly, P, Barroso, I, Blackwell, J M, Bramon, E, Brown, M A, Casas, J P, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H S, Mathew, C G, Palmer, C N A, Plomin, R, Rautanen, A, Sawcer, S J, Trembath, R, Viswanathan, A C, Wood, N W, Spencer, C C A, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, Langford, C, Hunt, S E, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, S J, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, O T, Liddle, J, Potter, S C, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, Mathew, C G, Blackwell, J M, Brown, M A, Corvin, A, Mccarthy, M I & Spencer, C C A 2014, ' Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins ', Nature Communications, vol. 5, 5068 . https://doi.org/10.1038/ncomms6068
- Accession number :
- edsair.doi.dedup.....21c332c6aa50f942d32d866b13c61827