Venexia MacLean Walker

Venexia MacLean Walker
University of Bristol | UB · MRC Integrative Epidemiology Unit

MMath

About

39
Publications
2,856
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387
Citations
Introduction
I am currently a senior research associate at the University of Bristol Medical Research Council Integrative Epidemiology Unit (MRC IEU), UK. In this role, I explore risk factors and potential intervention targets for chronic kidney disease progression. I recently submitted my PhD thesis titled ‘New uses for old drugs: Investigating whether antihypertensives can be repurposed for the prevention of dementia’ to the University of Bristol, UK. During my PhD, I took a six-month secondment to work at GlaxoSmithKline plc to investigate the use of genetic evidence in target validation. My research interests include pharmacoepidemiology and instrumental variable analysis.
Additional affiliations
October 2015 - April 2019
University of Bristol
Position
  • PhD Student

Publications

Publications (39)
Article
statistics for genome-wide association studies (GWAS) are increasingly available for downstream analyses. Meanwhile, the popularity of casual inference methods has grown as we look to gather robust evidence for novel medical and public health interventions. This has led to the development of methods that use GWAS summary statistics for causal infer...
Article
Full-text available
Aims/hypothesis Metformin use has been associated with reduced incidence of dementia in diabetic individuals in observational studies. However, the causality between the two in the general population is unclear. This study uses Mendelian randomisation (MR) to investigate the causal effect of metformin targets on Alzheimer’s disease and potential ca...
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Background Maintaining a healthy lifestyle to reduce type 2 diabetes (T2D) risk is challenging and additional strategies for T2D prevention are needed. We evaluated several lipid control medications as potential therapeutic options for T2D prevention using tissue-specific predicted gene expression summary statistics in a two-sample Mendelian random...
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Aims/hypothesis Type 2 diabetes and atherosclerotic CVD share many risk factors. This study aimed to systematically assess a broad range of continuous traits to separate their direct effects on coronary and peripheral artery disease from those mediated by type 2 diabetes. Methods Our main analysis was a two-step Mendelian randomisation for mediati...
Preprint
Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors which influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease p...
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Traditionally, heritability has been estimated using family-based methods such as twin studies. Advancements in molecular genomics have facilitated the development of alternative methods that utilise large samples of unrelated or related individuals. Yet, specific challenges persist in the estimation of heritability such as epistasis, assortative m...
Article
Dementia is at present incurable. It is seen in a range of neurodegenerative diseases, the most common being Alzheimer’s disease (AD). The debilitating neurocognitive deficits develop over time and available treatments have limited effectiveness. It is of paramount and economic concern to identify new and safe possibilities for treatment. Current t...
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Background: There is some evidence that circulating blood lipids play a role in the development of Alzheimer's disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of deme...
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Mendelian randomization (MR) studies carried out among patients with a particular health condition should establish the genetic instrument influences the exposure in that subgroup, however this is normally investigated in the general population. Here, we investigated whether the genetic associations of four cis-acting C-reactive protein (CRP) varia...
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Background Type 2 diabetes and atherosclerotic cardiovascular disease share several risk factors. However, it is unclear whether the effect of these risk factors on liability to atherosclerotic cardiovascular disease is independent of their effect on liability to type 2 diabetes. Methods We performed univariate Mendelian randomization to quantify...
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Background: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. We leveraged large-scale gen...
Article
Objective We aimed to estimate the effect of blood pressure (BP) traits and BP-lowering medications (via genetic proxies) on peripheral artery disease. Approach and Results Genome-wide association studies summary statistics were obtained for BP, peripheral artery disease (PAD), and coronary artery disease. Causal effects of BP on PAD were estimate...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictor...
Preprint
Full-text available
Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Milli...
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Full-text available
Background: Hypertension in midlife is associated with increased risk of Alzheimer disease and vascular dementia in late life. In addition, some antihypertensive drugs have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose antihypertensive drugs for the prevention o...
Preprint
Full-text available
Introduction: Genome-wide association studies (GWASs) often adjust for covariates, correct for medication use, or select on medication users. If these summary statistics are used in two-sample Mendelian randomization analyses, estimates may be biased. We used simulations to investigate how GWAS adjustment, correction and selection affects these est...
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Mendelian randomization (MR) estimates the causal effect of exposures on outcomes by exploiting genetic variation to address confounding and reverse causation. This method has a broad range of applications, including investigating risk factors and appraising potential targets for intervention. MR-Base has become established as a freely accessible,...
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Full-text available
Mendelian randomization (MR) uses genetic information to strengthen causal inference concerning the effect of exposures on outcomes. This method has a broad range of applications, including investigating risk factors and appraising potential targets for intervention. MR-Base has become established as a freely accessible, online platform, which comb...
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Full-text available
Background: Evidence concerning the potential repurposing of antihypertensives for Alzheimer's disease prevention is inconclusive. We used Mendelian randomization, which can be more robust to confounding by indication and patient characteristics, to investigate the effects of lowering systolic blood pressure, via the protein targets of different a...
Preprint
Full-text available
The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in protein levels. Here, we estimated the effects of 1002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 ass...
Preprint
Full-text available
Introduction: There is evidence that hypertension in midlife can increase the risk of Alzheimer's disease and vascular dementia in late life. In addition, some treatments for hypertension have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose treatments for hypertens...
Preprint
Full-text available
Background: Evidence concerning the potential repurposing of antihypertensives for Alzheimer's disease prevention is inconclusive. We used Mendelian randomization, which can be more robust to confounding by indication and patient characteristics, to investigate the effects of lowering systolic blood pressure (SBP), via different antihypertensive dr...
Article
Full-text available
Background: Drugs for dementia have been available in England since 1997. Since their launch, there have been several changes to national guidelines and initiatives that may have influenced prescribing. These include changes in National Institute for Health and Care Excellence (NICE) guidance, several government dementia strategies, the addition o...
Article
Full-text available
Identification of unintended drug effects, specifically drug repurposing opportunities and adverse drug events, maximizes the benefit of a drug and protects the health of patients. However, current observational research methods are subject to several biases. These include confounding by indication, reverse causality and missing data. We propose th...
Article
Full-text available
Background: Instrumental variable analysis, for example with physicians' prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomization power calculat...
Preprint
Full-text available
Background: Drugs for dementia have been available in England from 1997. Since their launch, there have been several changes to national guidelines and initiatives that may have influenced prescribing. These include changes in National Institute for health and Care Excellence (NICE) guidance; several government dementia strategies; the addition of...
Preprint
Full-text available
Background: Drugs for dementia have been available in England from 1997. Since their launch, there have been several changes to national guidelines and initiatives that may have influenced prescribing. These include changes in National Institute for health and Care Excellence (NICE) guidance; several government dementia strategies; the addition of...
Article
Full-text available
Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective me...
Preprint
Full-text available
Background Instrumental variable analysis, for example with physicians’ prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomisation power calculator...

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Project (1)
Project
To use instrumental variable analysis methods, in existing data sources, to triangulate evidence for repurposing antihypertensive drugs for the prevention of dementia.