Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Year: 2020
Type: review
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. 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.
DOI: 10.17615/b2qf-7d72
Authors: de Craen, Anton J. M., Chasman, Daniel I., Poulter, Neil, Postmus, Iris, de Keyser, Catherine E., Stott, David J., Avery, Christy L., Donnelly, Louise A., Barnes, Michael R., Johnson, Andrew D., Deshmukh, Harshal A., Zhou, Kaixin, Buckley, Brendan M., Evans, Daniel S., Li, Guo, Eline Slagboom, P., Wiggins, Kerri L., Sattar, Naveed, Shields, Denis C., Warren, Helen R., Munroe, Patricia B., Taylor, Kent D., Westendorp, Rudi G. J., Sever, Peter, Li, Xiaohui, Trompet, Stella, Arsenault, Benoit J., Feng, QiPing, Smith, Albert V., Ford, Ian, Griffin, Paula, Stanton, Alice
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Bristol-Myers Squibb, Pfizer, AstraZeneca, Wake Forest University, School of Medicine, Boston University, Johns Hopkins University, Wellcome Trust, National Institute for Health and Care Research, Diabetes UK, Imperial College London, European Commission, ZonMw, Erasmus Universiteit Rotterdam, Erasmus Medisch Centrum, Hjartavernd, National Institutes of Health, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G100949702, G1023702118, G1028935811, G1052397333, WTCCC2 core activities., G1083180012, G1097528416, G1182793083, G119964413, G1224608327, G1243299691, G125972088, G1261793039, G1401438683, G1438302022, G1460387277, G1466586219, Estrogens and pharmacogenetic risks of venous thrombosis in postmenopausal women, G1527150935, G1614110324, G1691174148, UCLA Clinical and Translational Science Institute, G1726490033, G173303992, G1922428914, G1982334678, Genome-wide case-only study of antihypertensive drug-gene interactions, G2146332128, G2178492673, G2193588257, G2268671860, WTCCC2 core activities, G230712557, G2450915342, G2473961061, Institute for Clinical and Translational Research (UL1), G250621538, G2555954497, G2564988809, G2663518188, G270907595, G2786044735, G2800149121, G2815873878, G2818913090, G2830784186, G2918387404, G2973790809, G2989067737, G3007488127, G301743239, G3021948349, G3027556099, G3041236093, G3114902838, G3137375862, G3152385821, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, Pharmacogenomics and Risk of Cardiovascular Disease, Atrial Fibrillation: Incidence, Risk Factors, and Genetics, G3205625555, G3207356259, G3220743633, G322252321, G3244135850, UCLA Clinical and Translational Science Institute, G3402222819, G34347772, G3462919067, G3692229207, G36937976, G3721894273, GWA for Gene-Environment Interaction Effects Influencing CHD, G3738692396, G3860090032, G3884610240, G393177772, G4167445418, G4200864717, G4219624527, G423252844, G4577178459, G4599028518, G4622379297, G4660668308, G4685761485, G4765588100, G4824283243, Therapeutic immunomodulation in dengue with hyperinflammation, G4942589162, G4998334444, G503914490, G5053595415, G5074086979, G5075046117, G5096014916, G5145575165, G5206110354, G5251985303, G5253921404, G5281659474, G5333949756, G537455924, G5386252567, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G544148272, G5479317095, G5488312170, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5622977475, G563474107, G567847597, G5702163051, G573134505, G5755700318, G5778869478, G581554933, G5868276417, CHARGE consortium: omics discovery for CVD and aging phenotypes, G6007406412, G6033034647, G6195637971, G6198607424, G6401035755, G6552090923, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G6706757010, G670738241, G6832344490, G6902273418, G7007046788, G7051404557, G7093047072, WTCCC2 core activities., G7217924807, G7244861316, G7372409674, G7373387228, G7406331046, G7505613430, G7603769780, G764651519, G766700449, G766843672, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G777822606, G781162660, A PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease, G7908261463, G7955974312, G80149192, G806768229, G8068269535, G820615960, G8213835172, G824087253, G8260701975, G8506930532, G8541424066, G861947890, CHS-Transition Phase -268055222, G8716920314, G88852782, G8892155751, G9000027259, G9000033427, G9000046001, G9000065698, G9000069887, G9000124008, G9000124674, G9000139054, G9000140433, G9000155215, G9000294005, G9000300101, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G991334795
OpenAlex ID: W4300424280