Comparing the Relationships of Genetically Proxied PCSK9 Inhibition With Mood Disorders, Cognition, and Dementia Between Men and Women: A Drug-Target Mendelian Randomization Study

Review Cardiac & Cardiovascular Systems

Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials

Paul Guedeney et al.

Summary: Treatment with alirocumab or evolocumab is associated with reduced risk of myocardial infarction, stroke, and coronary revascularization, with a favorable safety profile.

EUROPEAN HEART JOURNAL (2022)

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Article Biochemistry & Molecular Biology

Meta-GWAS of PCSK9 levels detects two novel loci at APOB and TM6SF2

Janne Pott et al.

Summary: This study identified novel genetic loci affecting PCSK9 levels and confirmed ethnic heterogeneity at the PCSK9 locus. While the causal effect of PCSK9 on CAD is mainly mediated by LDL-C, an independent direct effect also occurs.

HUMAN MOLECULAR GENETICS (2022)

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Article Cardiac & Cardiovascular Systems

Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function

Daniel B. Rosoff et al.

Summary: This genetics-based study found that long-term PCSK9 inhibition had a neutral cognitive profile, while HMGCR inhibition had adverse effects on cognitive performance, reaction time, and cortical surface area. Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer's disease progression or Lewy body dementia risk.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2022)

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Article Multidisciplinary Sciences

Mendelian randomization

Eleanor Sanderson et al.

Summary: Mendelian randomization (MR) uses genetic variation to address causal questions about modifiable exposures, with principles based on Mendel's laws and instrumental variable estimation methods. It enables inference of causal effects and can be used as part of a triangulation across multiple sources of evidence for causal inference.

NATURE REVIEWS METHODS PRIMERS (2022)

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Letter Medicine, General & Internal

PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study

Donald M. Lyall et al.

Summary: The study found an association between lower CHD risk and PCSK9 allele score, but also weakly linked it with worse reaction time, suggesting a potential relationship between PCSK9 genetic variants and cognitive function.

ARCHIVES OF MEDICAL SCIENCE (2021)

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Article Cardiac & Cardiovascular Systems

Genetic Liability to Depression and Risk of Coronary Artery Disease, Myocardial Infarction, and Other Cardiovascular Outcomes

Yunlong Lu et al.

Summary: The genetic liability to depression is associated with higher risks of coronary artery disease (CAD) and myocardial infarction, partly mediated by type 2 diabetes mellitus and smoking.

JOURNAL OF THE AMERICAN HEART ASSOCIATION (2021)

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Article Multidisciplinary Sciences

The power of genetic diversity in genome-wide association studies of lipids

Sarah E. Graham et al.

Summary: This study conducted a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. The findings demonstrate that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction, with modest gains in the number of discovered loci and ancestry-specific variants. This highlights the importance of including diverse populations in genetic studies to improve the accuracy and equity of polygenic scores in clinical practice.

NATURE (2021)

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Review Cardiac & Cardiovascular Systems

Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development

Michael V. Holmes et al.

Summary: This article discusses the discovery and evaluation process of drug targets for cardiovascular disease, emphasizing the importance of using Mendelian randomization to establish causation.

NATURE REVIEWS CARDIOLOGY (2021)

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Review Psychology, Clinical

Causal inference with observational data: the need for triangulation of evidence

Gemma Hammerton et al.

Summary: The goal of observational research is to identify risk factors affecting health and social outcomes, but biases in observational data can lead to underestimation or overestimation of effects. Advanced statistical techniques can address some biases, but design-based approaches are also important, as no single method can provide a definitive answer to causal questions.

PSYCHOLOGICAL MEDICINE (2021)

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Article Multidisciplinary Sciences

In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates

Kiran Musunuru et al.

Summary: This study demonstrates the efficient and precise modification of disease-related genes in living cynomolgus monkeys using CRISPR base editors delivered in vivo via lipid nanoparticles. The results provide proof-of-concept for the potential therapeutic application of CRISPR base editors in making precise single-nucleotide changes in target genes, supporting a 'once-and-done' approach for the treatment of diseases.

NATURE (2021)

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Article Biotechnology & Applied Microbiology

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

Tanja Rothgangl et al.

Summary: ABEs have been shown to effectively and safely reduce LDL levels in the livers of mice and cynomolgus macaques. Using lipid nanoparticle-based delivery of mRNA encoding an ABE and a sgRNA targeting PCSK9, significant reductions in PCSK9 and LDL levels were achieved in both species. Further research is warranted to explore the potential of ABEs in treating monogenic liver diseases.

NATURE BIOTECHNOLOGY (2021)

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Article Cardiac & Cardiovascular Systems

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults

Zhen Zhou et al.

Summary: The study found that statin therapy in adults aged 65 and older was not associated with incident dementia, MCI, or declines in individual cognition domains. The impact of statin lipophilicity and baseline neurocognitive ability on these associations was also explored. Further confirmation from ongoing randomized trials is needed.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2021)

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Article Medicine, General & Internal

Analysis of Female Enrollment and Participant Sex by Burden of Disease in US Clinical Trials Between 2000 and 2020

Jecca R. Steinberg et al.

Summary: This study found that sex differences in clinical trials varied by disease category, with male and female participants underrepresented in different medical fields. Although progress has been made in sex equity, the persistence of sex bias in clinical trials within medical fields has negative consequences for the health of all individuals.

JAMA NETWORK OPEN (2021)

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Article Biochemistry & Molecular Biology

Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort

Golam M. Khandaker et al.

MOLECULAR PSYCHIATRY (2020)

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Article Clinical Neurology

Lipid Lowering and Alzheimer Disease Risk: A Mendelian Randomization Study

Dylan M. Williams et al.

ANNALS OF NEUROLOGY (2020)

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Article Medicine, General & Internal

Association Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer

James Yarmolinsky et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Endocrinology & Metabolism

Major depressive disorder and cardiometabolic diseases: a bidirectional Mendelian randomisation study

Bowen Tang et al.

DIABETOLOGIA (2020)

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Article Medicine, General & Internal

Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol

Kausik K. Ray et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Medicine, General & Internal

Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia

Frederick J. Raal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Review Neurosciences

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in the Brain and Relevance for Neuropsychiatric Disorders

Emma M. O'Connell et al.

FRONTIERS IN NEUROSCIENCE (2020)

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Article Pediatrics

Hyperlipidemia

Jeremy Stewart et al.

PEDIATRICS IN REVIEW (2020)

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Article Multidisciplinary Sciences

Genetic drug target validation using Mendelian randomisation

Amand F. Schmidt et al.

NATURE COMMUNICATIONS (2020)

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Article Medicine, General & Internal

Evinacumab for Homozygous Familial Hypercholesterolemia

Frederick J. Raal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Review Neurosciences

Sex differences in depression: Insights from clinical and preclinical studies

Rand S. Eid et al.

PROGRESS IN NEUROBIOLOGY (2019)

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Article Pharmacology & Pharmacy

Gender Differences in Response to PCSK9 Inhibitor Therapy

Paul Ziajka

Journal of Clinical Lipidology (2019)

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Article Clinical Neurology

LDL cholesterol relates to depression, its severity, and the prospective course

Claudia Johanna Wagner et al.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2019)

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Article Endocrinology & Metabolism

Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: The ORION-1 Randomized Clinical Trial

Lawrence A. Leiter et al.

DIABETES CARE (2019)

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Review Cardiac & Cardiovascular Systems

PCSK9 inhibitors: clinical evidence and implementation

Marc S. Sabatine

NATURE REVIEWS CARDIOLOGY (2019)

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Article Public, Environmental & Occupational Health

Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption

Jack Bowden et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2019)

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Article Clinical Neurology

Gender differences in subtypes of depression by first incidence and age of onset: a follow-up of the Lundby population

Mats Bogren et al.

EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE (2018)

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Article Biochemistry & Molecular Biology

Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder

F. W. Lohoff et al.

MOLECULAR PSYCHIATRY (2018)

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Review Biochemistry & Molecular Biology

Evaluating the potential role of pleiotropy in Mendelian randomization studies

Gibran Hemani et al.

HUMAN MOLECULAR GENETICS (2018)

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Article Clinical Neurology

Risk of Neuropsychiatric Adverse Effects of Lipid-Lowering Drugs: A Mendelian Randomization Study

Jahad Alghamdi et al.

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY (2018)

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Article Neurosciences

Differences Between Women and Men in Incidence Rates of Dementia and Alzheimer's Disease

Christopher R. Beam et al.

JOURNAL OF ALZHEIMERS DISEASE (2018)

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Article Biology

The MR-Base platform supports systematic causal inference across the human phenome

Gibran Hemani et al.

ELIFE (2018)

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Editorial Material Physiology

Hyperlipidemia in Stroke Pathobiology and Therapy: Insights and Perspectives

Romain Menet et al.

FRONTIERS IN PHYSIOLOGY (2018)

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Editorial Material Cardiac & Cardiovascular Systems

Nonstatin Therapy for Dyslipidemia Current and Future Directions

Haitham M. Ahmed et al.

CIRCULATION RESEARCH (2018)

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Article Medicine, General & Internal

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

G. G. Schwartz et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Public, Environmental & Occupational Health

MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data

Olena O. Yavorska et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2017)

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Article Cardiac & Cardiovascular Systems

Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab Pooled Data From Randomized Trials

Jennifer G. Robinson et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2017)

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Editorial Material Cardiac & Cardiovascular Systems

REVEALing the effect of CETP inhibition in cardiovascular disease

Michael V. Holmes et al.

NATURE REVIEWS CARDIOLOGY (2017)

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Article Medicine, General & Internal

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

Marc S. Sabatine et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Article Mathematical & Computational Biology

A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization

Jack Bowden et al.

STATISTICS IN MEDICINE (2017)

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Article Genetics & Heredity

Orienting the causal relationship between imprecisely measured traits using GWAS summary data

Gibran Hemani et al.

PLOS GENETICS (2017)

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Article Public, Environmental & Occupational Health

Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population

Anna Fry et al.

AMERICAN JOURNAL OF EPIDEMIOLOGY (2017)

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Article Cardiac & Cardiovascular Systems

Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapyA cognitive study of patients enrolled in the FOURIER trial

Robert P. Giugliano et al.

CLINICAL CARDIOLOGY (2017)

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Article Cardiac & Cardiovascular Systems

Heart Disease and Stroke Statistics-2016 Update A Report From the American Heart Association

Dariush Mozaffarian et al.

CIRCULATION (2016)

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Article Genetics & Heredity

Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator

Jack Bowden et al.

GENETIC EPIDEMIOLOGY (2016)

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Article Genetics & Heredity

Bias due to participant overlap in two-sample Mendelian randomization

Stephen Burgess et al.

GENETIC EPIDEMIOLOGY (2016)

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Article Public, Environmental & Occupational Health

Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic

Jack Bowden et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2016)

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Article Cardiac & Cardiovascular Systems

Prognosis of Variant Angina Manifesting as Aborted Sudden Cardiac Death

Jung-Min Ahn et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2016)

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Article Public, Environmental & Occupational Health

Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects

Stephen Burgess et al.

AMERICAN JOURNAL OF EPIDEMIOLOGY (2015)

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Article Public, Environmental & Occupational Health

Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression

Jack Bowden et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2015)

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Review Pharmacology & Pharmacy

Serotonin pathway polymorphisms and the treatment of major depressive disorder and anxiety disorders

Sarah G. Helton et al.

PHARMACOGENOMICS (2015)

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Article Multidisciplinary Sciences

The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

Kristin G. Ardlie et al.

SCIENCE (2015)

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Article Behavioral Sciences

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats

Xu Hu et al.

BEHAVIORAL AND BRAIN FUNCTIONS (2014)

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Article Biochemistry & Molecular Biology

Mendelian randomization: genetic anchors for causal inference in epidemiological studies

George Davey Smith et al.

HUMAN MOLECULAR GENETICS (2014)

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Article Public, Environmental & Occupational Health

Calculating statistical power in Mendelian randomization studies

Marie-Jo A. Brion et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2013)

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Article Genetics & Heredity

Discovery and refinement of loci associated with lipid levels

Cristen J. Willer et al.

NATURE GENETICS (2013)

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Editorial Material Genetics & Heredity

The Genotype-Tissue Expression (GTEx) project

John Lonsdale et al.

NATURE GENETICS (2013)

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Review Pharmacology & Pharmacy

Pharmacogenetics of antidepressant drugs: current clinical practice and future directions

Sneha Narasimhan et al.

PHARMACOGENOMICS (2012)

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Article Public, Environmental & Occupational Health

Avoiding bias from weak instruments in Mendelian randomization studies

Stephen Burgess et al.

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY (2011)

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Article Pharmacology & Pharmacy

Changes in Memory Function and Neuronal Activation Associated with Atorvastatin Therapy

Beth A. Parker et al.

PHARMACOTHERAPY (2010)

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Article Pharmacology & Pharmacy

Statin-Associated Adverse Cognitive Effects: Survey Results from 171 Patients

Marcella A. Evans et al.

PHARMACOTHERAPY (2009)

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Article Psychiatry

Sex differences in depression symptoms in treatment-seeking adults: confirmatory analyses from the Sequenced Treatment Alternatives to Relieve Depression study

Sheila M. Marcus et al.

COMPREHENSIVE PSYCHIATRY (2008)

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Article Health Care Sciences & Services

Mendelian randomization as an instrumental variable approach to causal inference

Vanessa Didelez et al.

STATISTICAL METHODS IN MEDICAL RESEARCH (2007)

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Article Primary Health Care

Hyperlipidemia

CB Eaton

PRIMARY CARE (2005)

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Review Biochemistry & Molecular Biology

Atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime

D Steinberg

NATURE MEDICINE (2002)

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Comparing the Relationships of Genetically Proxied PCSK9 Inhibition With Mood Disorders, Cognition, and Dementia Between Men and Women: A Drug-Target Mendelian Randomization Study

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