Alison Murray

Alison Murray
University of Aberdeen | ABDN · Aberdeen Biomedical Imaging Centre

MBChB, MRCP, FRCR, FRCP, PhD

About

308
Publications
39,881
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8,381
Citations
Citations since 2017
186 Research Items
5474 Citations
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201720182019202020212022202302004006008001,0001,200
201720182019202020212022202302004006008001,0001,200
201720182019202020212022202302004006008001,0001,200
Additional affiliations
January 2002 - present
University of Aberdeen
Description
  • Neuroradiology lead for Aberdeen Birth Cohort studies and Director Aberdeen Biomedical Imaging Centre

Publications

Publications (308)
Article
Full-text available
Background DNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease. However, the molecular mechanisms under...
Article
Full-text available
Background Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample...
Article
Full-text available
Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence,...
Article
Full-text available
Background Fatigue is a common and burdensome symptom in Rheumatoid Arthritis (RA), yet is poorly understood. Currently, clinicians rely solely on fatigue questionnaires, which are inherently subjective measures. For the effective development of future therapies and stratification, it is of vital importance to identify biomarkers of fatigue. In thi...
Preprint
Introduction Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brai...
Article
Full-text available
Background: Radiomics is the high throughput analysis of medical images using computer algorithms, which specifically assess textural features. It has increasingly been proposed as a tool for the development of imaging biomarkers. However, an important acknowledged limitation of radiomics is the lack of reproducibility of features produced. Purpo...
Article
Full-text available
The Aberdeen birth cohorts of 1921 and 1936 (ABC21 and ABC36) were subjected to IQ tests in 1932 or 1947 when they were aged about 11y. They were recruited between 1997–2001 among cognitively healthy community residents and comprehensively phenotyped in a long-term study of brain aging and health up to 2017. Here, we report associations between bas...
Article
Introduction Haemoglobin concentrations decrease with age. Abnormally low and high haemoglobin concentrations are associated with reduced cognition; however, the evidence for these associations in cohort data is limited. This study aims to assess the relationship between haemoglobin concentration and cognition in a well-characterised cohort of olde...
Article
Background: Crossed cerebellar diaschisis (CCD) is characterized by hypometabolism and hypoperfusion on molecular imaging in the cerebellum due to a supratentorial lesion on the contralateral side. CCD is a well-established phenomenon in acute or subacute conditions such as infarction but it has been less well described in chronic conditions such...
Article
Full-text available
Background Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. Results Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% o...
Preprint
Background: Major Depressive Disorder (MDD) is associated with negative affective cognitive biases. Differences on population level however remain unclear, including whether they normalise with remission. This study investigated associations between affective cognition and MDD within a large community-based sample.Methods: Participants from Generat...
Article
Full-text available
The behavioural variant of frontotemporal dementia is a clinical syndrome characterised by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving ri...
Article
Full-text available
A complex interplay of genetic and environmental risk factors influence global brain structural alterations associated with brain health and disease. Epigenome-wide association studies (EWAS) of global brain imaging phenotypes have the potential to reveal the mechanisms of brain health and disease and can lead to better predictive analytics through...
Preprint
Full-text available
Background Fatigue is a common and burdensome symptom in Rheumatoid Arthritis (RA), yet is poorly understood. Currently, clinicians rely solely on fatigue questionnaires, which are inherently subjective measures. For the effective development of future therapies and stratification, it is of vital importance to identify biomarkers of fatigue. In thi...
Article
Full-text available
Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight),...
Preprint
Full-text available
Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, bir...
Article
Full-text available
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We...
Article
Full-text available
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of Europe...
Article
Full-text available
There is increasing interest in using data-driven unsupervised methods to identify structural underpinnings of common mental illnesses, including Major Depressive Disorder (MDD) and associated traits such as cognition. However, studies are often limited to severe clinical cases with small sample sizes and most do not include replication. Here, we e...
Article
Full-text available
Alcohol use and smoking are leading causes of death and disability worldwide. Both genetic and environmental factors have been shown to influence individual differences in the use of these substances. In the present study we tested whether genetic factors, modelled alongside common family environment, explained phenotypic variance in alcohol use an...
Article
Full-text available
STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS pro...
Preprint
Full-text available
DNA methylation is an epigenetic mark associated with gene repression and genome stability. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Rates of aging inferred from these clocks correlate with human health. However, the molecular mechanisms underpinning age-assoc...
Article
Full-text available
Objectives Positron emission tomography–magnetic resonance imaging (PET/MRI) is an emerging hybrid imaging system in clinical nuclear medicine. Research demonstrates a comparative utility to current unimodal and hybrid methods, including PET-computed tomography (PET/CT), in several medical subspecialities such as neuroimaging. The aim of this revie...
Preprint
Full-text available
Using blood-based epigenome-wide analyses of general cognitive function (g; n=9,162) we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in g. A DNAm predictor explains ~4% of the variance in g, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurolog...
Article
Full-text available
Alzheimer's disease (AD) is the most common cause of dementia and accounts for approximately 50% to 80% of all cases of dementia. The diagnosis of probable AD is based on clinical criteria and overlapping clinical features pose a challenge to accurate diagnosis. However, neuroimaging has been included as a biomarker in various published criteria fo...
Article
Full-text available
Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by...
Preprint
Full-text available
Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry...
Article
Full-text available
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10⁻⁸), of which 32 were in new BP-associated loci...
Article
Reduced cortical structural properties are recognised as potential imaging marker for neurodegenerative disorders. However, networks of correlated fluctuations in cortical structural properties in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD) have remained elusive. Here, we set out to investigate organisations of...
Poster
Objective: The successful creation and evaluation of AI solutions in healthcare depends on two main factors; access to large validated datasets, and the safe, well governed, and anonymised storage of that data. Most epidemiological studies depend on access to such data, however, with the recent advances in computing power and the emergence of AI,...
Preprint
Full-text available
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We presen...
Article
Background Our understanding of the potential harm of taking multiple medications in older, multi-morbid populations is limited. We aimed to investigate the prevalence of polypharmacy and its association with hospitalisation in a large cohort with linked health data. Methods Prescription data and hospital admission records of the Aberdeen Children...
Article
Full-text available
Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods We constructed a polygenic risk score using a genome-wide assoc...
Article
Full-text available
Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previ...
Article
Full-text available
A high rate of polypharmacy is, in part, a consequence of the increasing proportion of multimorbidity in the ageing population worldwide. Our understanding of the potential harm of taking multiple medications in an older, multi-morbid population, who are likely to be on a polypharmacy regime, is limited. This is a narrative literature review that a...
Article
Full-text available
Background The underlying mechanisms leading to dementia and Alzheimer's Disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population‐based evidence is lacking. Methods Change in cognitive performance was assessed in participants of the Aber...
Article
Full-text available
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have no...
Article
Full-text available
Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex....
Article
Full-text available
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on inciden...
Article
Full-text available
Background: Hydromethylthionine is a potent inhibitor of pathological aggregation of tau and TDP-43 proteins. Objective: To compare hydromethylthionine treatment effects at two doses and to determine how drug exposure is related to treatment response in bvFTD. Methods: We undertook a 52-week Phase III study in 220 bvFTD patients randomized to...
Article
Objectives: Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden a...
Article
Full-text available
Eating disorders and substance use disorders frequently co‐occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin‐based = 0.23‐0.53). We estimated the genetic correlation...
Article
Full-text available
Variation in the klotho gene is linked to differences in health outcomes: klotho allele KL-VS heterozygosity is associated with longevity, better cognition and greater right frontal grey matter volume in late life. Contradicting reports, however, suggest that KL-VS’s effect on health might be age-dependent. Here we examine the relationship between...
Article
Full-text available
Purpose Hyperintensities are common in neuroimaging scans of patients with mild acute focal neurology. However, their pathogenic role and clinical significance is not well understood. We assessed whether there was an association between hyperintensity score with diagnostic category and clinical assessments/measures. Methods One hundred patients (5...
Article
Full-text available
Background: Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in blood-based DNA meth...
Article
Full-text available
STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS pro...
Article
Full-text available
'Epigenetic age acceleration' is a valuable biomarker of ageing, predictive of morbidity and mortality, but for which the underlying biological mechanisms are not well established. Two commonly used measures, derived from DNA methylation, are Horvath-based (Horvath-EAA) and Hannum-based (Hannum-EAA) epigenetic age acceleration. We conducted genome-...
Article
Full-text available
Background The Aberdeen Children of the 1950s (ACONF) cohort contains 12,150 individuals born in Aberdeen, Scotland in the 1950s. The study includes rich early life data, information from questionnaire in middle age, and linkage to electronic healthcare records. Involving the participants in designing future data collection and research is key to...
Article
Full-text available
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding...
Article
Full-text available
Background: Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials in mild to moderate Alzheimer's disease (AD) comparing doses in the range 150-250 mg/day with 8 mg/day intended as a control. Objective: To determine how drug exposure is related to treatment response. Method...
Article
Full-text available
Objectives: White matter hyperintensities (WMH) are a common imaging finding indicative of cerebral small vessel disease. Lesion segmentation algorithms have been developed to overcome issues arising from visual rating scales. In this study, we evaluated two automated methods and compared them to visual and manual segmentation to determine the mos...
Article
Full-text available
Background: The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian...
Article
Full-text available
Background: DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed 'epigenetic clocks'. The deviation of predicted age from the actual age ('age acceleration residual', AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affe...
Preprint
Full-text available
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlati...
Article
Objective: Rheumatoid arthritis (RA) patients with comorbid fibromyalgia (FM) manifest alterations in brain connectivity synonymous with central sensitization. Here we consider how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with comorbid FM. Methods: RA patients with (FM+,...
Preprint
Full-text available
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality 1,2 . We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, disco...
Article
Objectives: Fatigue is a major burden among patients with RA, yet is poorly understood. We sought to conduct the first imaging study to investigate the neurobiological correlates of fatigue in RA and to improve upon the methodological limitations of previous neuroimaging studies that have investigated this symptom in other populations. Methods:...
Preprint
Full-text available
Introduction Advanced age is associated with cognitive and physical decline, and is a major risk factor for a multitude of disorders including neurodegenerative diseases such as Alzheimer’s disease. There is also a gap in life-expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. H...