Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study

ObjeCtive To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis( PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ), respectively) is associated with a high risk of Alzheimer’s disease, vascular dementia, any dementia, and Parkinson’s disease in the general population. in genetic complete data on age, sex, genotypes, and endpoints.

[1]  K. Bhaskaran,et al.  Impact of statin related media coverage on use of statins: interrupted time series analysis with UK primary care data , 2016, British Medical Journal.

[2]  G. Davey Smith,et al.  Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator , 2016, Genetic epidemiology.

[3]  A. Tybjærg‐Hansen,et al.  Using human genetics to predict the effects and side-effects of drugs , 2016, Current opinion in lipidology.

[4]  Hong Lu,et al.  Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis , 2016, PloS one.

[5]  B. Nordestgaard,et al.  Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. , 2016, European heart journal.

[6]  Jennifer G. Robinson,et al.  Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[7]  J. Karlawish,et al.  Statin Therapy and Risk of Acute Memory Impairment. , 2015, JAMA internal medicine.

[8]  R. Giugliano,et al.  Are PCSK9 Inhibitors the Next Breakthrough in the Cardiovascular Field? , 2015, Journal of the American College of Cardiology.

[9]  Jennifer G. Robinson,et al.  Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[10]  G. Davey Smith,et al.  Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression , 2015, International journal of epidemiology.

[11]  Xuemei Huang,et al.  Statins, plasma cholesterol, and risk of Parkinson's disease: A prospective study , 2015, Movement disorders : official journal of the Movement Disorder Society.

[12]  B. Nordestgaard,et al.  Plasma levels of apolipoprotein E and risk of dementia in the general population , 2015, Annals of neurology.

[13]  Hynek Pikhart,et al.  HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials , 2015, The Lancet.

[14]  T. Trikalinos,et al.  Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2015, Journal of General Internal Medicine.

[15]  D. Diamond,et al.  Examination of the FDA Warning for Statins and Cognitive Dysfunction , 2014 .

[16]  D. Rader,et al.  Statins and Cognitive Function: A Systematic Review†∗ , 2014 .

[17]  S. Burgess.  Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome , 2014, International journal of epidemiology.

[18]  B. Nordestgaard,et al.  Elevated body mass index as a causal risk factor for symptomatic gallstone disease: A Mendelian randomization study , 2013, Hepatology.

[19]  Tanya M. Teslovich,et al.  Discovery and refinement of loci associated with lipid levels , 2013, Nature Genetics.

[20]  A. Butterworth,et al.  Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data , 2013, Genetic epidemiology.

[21]  B. Nordestgaard,et al.  Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation , 2013, Circulation.

[22]  N. Sattar,et al.  PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population[S] , 2013, Journal of Lipid Research.

[23]  R. Collins,et al.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials , 2012, The Lancet.

[24]  N. Timpson,et al.  The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach , 2012, PLoS medicine.

[25]  John P A Ioannidis,et al.  What Should the Genome-wide Significance Threshold Be? Empirical Replication of Borderline Genetic Associations Yfor a Full List of Investigators Offering Data and Clarifications See Acknowledgments , 2022 .

[26]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[27]  M. Flather.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010 .

[28]  Vanessa Didelez,et al.  Assumptions of IV methods for observational epidemiology , 2010, 1011.0595.

[29]  B. Golomb,et al.  Statin‐Associated Adverse Cognitive Effects: Survey Results from 171 Patients , 2009, Pharmacotherapy.

[30]  G. Boysen,et al.  European Guidelines on Cardiovascular Disease Prevention , 2009, International journal of stroke : official journal of the International Stroke Society.

[31]  M. Kivipelto,et al.  Total cholesterol and the risk of Parkinson disease , 2008, Neurology.

[32]  Cholesterol Treatment Trialists' Collaborators.  Efficacy of cholesterol-lowering therapy in 18 686 people with diabetes in 14 randomised trials of statins: a meta-analysis , 2008, The Lancet.

[33]  R Peto,et al.  Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. , 2008, Lancet.

[34]  L. Kessing,et al.  Validity of Dementia Diagnoses in the Danish Hospital Registers , 2007, Dementia and Geriatric Cognitive Disorders.

[35]  Jonathan C. Cohen,et al.  Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. , 2006, American journal of human genetics.

[36]  L. Kuller,et al.  Statins and cognitive function in the elderly , 2005, Neurology.

[37]  J. Whitworth,et al.  2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension , 2003, Journal of hypertension.

[38]  J. Weissenbach,et al.  Mutations in PCSK9 cause autosomal dominant hypercholesterolemia , 2003, Nature Genetics.

[39]  Christopher F. Baum,et al.  Instrumental Variables and GMM: Estimation and Testing , 2003 .

[40]  S. Ebrahim,et al.  'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? , 2003, International journal of epidemiology.

[41]  R. Frikke-Schmidt,et al.  APOE genotype predicts AD and other dementia but not ischemic cerebrovascular disease , 2001, Neurology.

[42]  P. Macfarlane,et al.  Pravastatin and cognitive function in the elderly. Results of the PROSPER study , 2009, Journal of Neurology.

[43]  P. Arora,et al.  Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients. , 2008, The American journal of medicine.

[44]  George Davey Smith,et al.  Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology , 2008, Statistics in medicine.

[45]  Eric Boerwinkle,et al.  Sequence Variations in PCSK 9 , Low LDL , and Protection against Coronary Heart Disease , 2006 .

[46]  Elinor Miller,et al.  Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). , 2003, The American journal of cardiology.