A5089679358- Genetic Associations and Epidemiology
- Lipoproteins and Cardiovascular Health
- Genomics and Rare Diseases
- Cardiovascular Function and Risk Factors
- Bioinformatics and Genomic Networks
- Nuclear Receptors and Signaling
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Prenatal Screening and Diagnostics
- Alzheimer's disease research and treatments
- Computational Drug Discovery Methods
- Metabolism, Diabetes, and Cancer
- GDF15 and Related Biomarkers
- Cytokine Signaling Pathways and Interactions
- Cardiovascular Effects of Exercise
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Mapping and Diversity in Plants and Animals
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Coronary Artery Anomalies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Congenital Anomalies and Fetal Surgery
- Medical Coding and Health Information
- Down syndrome and intellectual disability research
- Health, Environment, Cognitive Aging
- RNA modifications and cancer
University College London
2017-2025
British Heart Foundation
2020-2024
King Abdulaziz University
2023
UCL Biomedical Research Centre
2023
Farr Institute
2017
Indian Institute of Technology Kanpur
2012-2014
Mendelian randomisation (MR) analysis is an important tool to elucidate the causal relevance of environmental and biological risk factors for disease. However, inference undermined if genetic variants used instrument a factor also influence alternative disease-pathways (horizontal pleiotropy). Here we report how 'no horizontal pleiotropy assumption' strengthened when proteins are interest. Proteins typically proximal effectors processes encoded in genome. Moreover, targets most medicines, so...
Abstract Lack of efficacy in the intended disease indication is major cause clinical phase drug development failure. Explanations could include poor external validity pre-clinical (cell, tissue, and animal) models human high false discovery rate ( FDR ) preclinical science. related to proportion true relationships available for γ ), type 1 (false-positive) 2 (false negative) error rates experiments designed uncover them. We estimated science, its effect on success rates, improvements...
Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups younger people. We estimated the frequency common disease combinations identified non-random associations all ages in multiethnic population.In this population-based study, we examined patterns stratified by ethnicity or race, sex, age 308 health conditions using electronic records from individuals included on Clinical Practice Research Datalink linked with Hospital Episode Statistics...
Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity mortality. We performed a genome-wide association study (GWAS) 16 cardiac magnetic resonance (CMR) imaging measurements biventricular function structure.
CETP inhibitors are a class of lipid-lowering drugs in development for treatment coronary heart disease (CHD). Genetic studies East Asian ancestry have interpreted the lack signal with low-density lipoprotein cholesterol (LDL-C) and drug target Mendelian randomization (MR) effect on CHD as evidence that might not be effective participants. Capitalizing recent increases sample size genetic studies, we conducted MR analysis, scaled to standard deviation increase high-density cholesterol....
Abstract Background Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites proteins associating with disease. Methods Mendelian randomisation (MR) was used assess association 174 measured up 86,507 participants AF, HF, dilated cardiomyopathy (DCM), non-ischemic (NICM). Subsequently, we sourced data on 1567 performed cis MR affecting identified well diseases. Proteins...
Abstract Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding drug target, that alter the target’s expression function, as tool to anticipate effect of action on same target. Here we apply MR prioritize targets for their causal relevance coronary heart disease (CHD). The are further prioritized using independent replication, co-localization, protein profiles and data from British National Formulary clinicaltrials.gov. Out 341 identified...
<h3>Background</h3> There has been considerable interest in statins due to their pleiotropic effects beyond lipid-lowering properties. Many of these are predominantly ascribed Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed genetically investigate the role lipids and statin interventions on multiple sclerosis (MS) risk severity. <h3>Method</h3> employed two-sample Mendelian randomization (MR) investigate: (1) causal mimic both cholesterol-dependent (via low-density...
Summary paragraph Heart failure (HF), a syndrome of symptomatic fluid overload due to cardiac dysfunction, is the most rapidly growing cardiovascular disorder. Despite recent advances, mortality and morbidity remain high treatment innovation challenged by limited understanding aetiology in relation disease subtypes. Here we harness de-confounding properties genetic variation map causal biology underlying HF phenotypic spectrum, inform development more effective treatments. We report...
Abstract Mendelian randomisation analysis has emerged as an important tool to elucidate the causal relevance of a range environmental and biological risk factors for human disease. However, inference on cause is undermined if genetic variants used instrument factor interest also associate with other traits that open alternative pathways disease (horizontal pleiotropy). We show how ‘no horizontal pleiotropy assumption’ in MR strengthened when proteins are interest. Proteins proximal effectors...
Abstract The direct causes of neurodegeneration underlying Alzheimer’s disease (AD) and many other dementias, are not known. Here we identify serum amyloid P component (SAP), a constitutive plasma protein normally excluded from the brain, as potential drug target. After meta-analysis three genome-wide association studies, comprising 44,288 participants, cis -Mendelian randomization showed that genes responsible for higher SAP values significantly associated with AD, Lewy body dementia tau...
Rearrangements between homologous chromosomes are extremely rare and manifest mainly as monosomic or trisomic offsprings. There remarkably few reports of balanced chromosomal translocation t (22q; 22q) only two cases transmission this homohologous rearrangement from mother to normal daughter reported. Robersonian carriers in non-homologous have the ability an unaffected child. However, it is not possible child with translocations chromosomes. Carriers chromosome 22 maternal uniparental...
Abstract Introduction Urinary breakdown products, representing kidney regulated filtration of metabolism end contain cardiac disease biomarkers such as NT-proBNP. We set out to integrate plasma proteins with pathways, reflected by urinary identify potentially druggable pathways for disease. Methods Data was leveraged from a genome-wide association study (GWAS) on 954 products. Mendelian randomisation used products associating atrial fibrillation (AF), heart failure (HF), dilated...
Abstract Background Heart failure (HF) represents a multifactorial clinical syndrome with differential response to existing therapies across its subtypes. Proteogenomic analysis of genetic variants associated changes in circulating protein level and risk heart subtypes provides an opportunity for systematic identification proteins subtype-specific causal effects as novel therapeutic targets. Purpose To identify potential targets specific by leveraging proteomics genomics data population...
<title>Abstract</title> CETP is a lipid drug target under development for coronary heart disease (CHD) in both European and East Asian populations. Previous Mendelian randomization (MR) studies conducted Asians failed to show CHD effect, which has been interpreted as lack of effectiveness inhibition prevention this population. Nevertheless, inhibitors are currently being evaluated participants. Capitalizing on recent increases sample size GWAS, we therefore MR estimate compare...
Introduction: Chromosomal Heteromorphisms are the inherited variations at specific chromosomal regions without a proven impact on phenotype of an individual. Material and Methods:We studied compared chromosome in Karyotypes two groups.The first group consisted 320 individuals 160 couples with more than miscarriages no live birth second 412 206 normal 1 child birth.Results discussion: Twenty Nine (9.06%) history recurrent pregnancy loss were found to have heteromorphisms, whereas thirteen...
Abstract Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity increased mortality. We performed a genome-wide association study (GWAS) 16 measurements biventricular function structure obtained from cardiac magnetic resonance (CMR). then used aggregated data three independent plasma proteome GWAS, cis- Mendelian randomization (MR) identify proteins with likely causal effect on traits. The subset robust CMR were prioritized through linkage...
Abstract Background There has been considerable interest in statins due to their pleiotropic effects beyond lipid-lowering properties. Many of these are predominantly ascribed capacity inhibit the isoprenylation Rho small guanosine triphosphatases (Rho GTPases). We aimed genetically investigate role lipids and statin interventions on multiple sclerosis (MS) risk severity. Method employed two-sample Mendelian randomization (MR) to: (1) causal (high-density lipoprotein cholesterol (HDL-C)...