A5072729258- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Bipolar Disorder and Treatment
- Genomics and Rare Diseases
- Wnt/β-catenin signaling in development and cancer
- Folate and B Vitamins Research
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- Advanced Queuing Theory Analysis
- Dementia and Cognitive Impairment Research
- Remote Sensing in Agriculture
- Health, Environment, Cognitive Aging
- Probability and Risk Models
- Genetic Syndromes and Imprinting
- Adolescent and Pediatric Healthcare
- Genetics and Neurodevelopmental Disorders
- Fractional Differential Equations Solutions
- Stochastic processes and financial applications
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Nutrition and Health in Aging
- Genomic variations and chromosomal abnormalities
- Leaf Properties and Growth Measurement
- Diet and metabolism studies
Cardiff University
2016-2025
UK Dementia Research Institute
2020-2025
University College London
2023
Medical Research Council
2017-2020
Genomics (United Kingdom)
2020
Swansea University
2012-2013
Universitat de València
2012
Polygenic Risk Scores (PRS) for AD offer unique possibilities reliable identification of individuals at high and low risk AD. However, there is little agreement in the field as to what approach should be used genetic score calculations, how model effect APOE, optimal p-value threshold (pT) SNP selection compare scores between studies methods. We show that best prediction accuracy achieved with a two predictors (APOE PRS excluding APOE region) pT<0.1 selection. Prediction sample across...
Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests amyloid tau pathology, as well neurodegeneration astrocytic activation. To define disease with rather than clinical assessment, we assessed prediction of research-diagnosed status using these tested genetic variants associated that may reflect more accurately risk biochemically defined instead dementia. In a cohort cases [n =...
Abstract: Lookup-table (LUT)-based radiative transfer model inversion is considered a physically-sound and robust method to retrieve biophysical parameters from Earth observation data but regularization strategies are needed mitigate the drawback of ill-posedness. We systematically evaluated various options improve leaf chlorophyll content (LCC) area index (LAI) retrievals over agricultural lands, including role (1) cost functions (CFs); (2) added noise; (3) multiple solutions in LUT-based...
Inversion of radiative transfer models (RTM) using a lookup-table (LUT) approach against satellite reflectance data can lead to concurrent retrievals biophysical parameters such as leaf chlorophyll content <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(Chl)$</tex></formula> and area index (LAI), but optimization strategies are not consolidated yet. ESA's upcoming satellites Sentinel-2 (S2)...
Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed understand the underlying disease processes mechanisms.
Alzheimer disease (AD) is the most common form of dementia and responsible for a huge growing health care burden in developed developing world. The polygenic risk score (PRS) approach has shown 75 to 84% prediction accuracy identifying individuals with AD risk.In this study, we tested AD, mild cognitive impairment (MCI), amyloid deposition risks PRS, including excluding APOE genotypes large publicly available dataset extensive phenotypic data, Alzheimer's Disease Neuroimaging Initiative...
Introduction Both late-onset Alzheimer’s disease (AD) and ageing have a strong genetic component. In each case, many associated variants been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based could explain differences reported heritability. Methods We compute five large independent cohorts (N = 7,396, 1,566, 803, 12,528 3,963) determine whether consensus for AD estimate can reached. These vary by sample size, age...
Abstract Background The success of selecting high risk or early-stage Alzheimer’s disease individuals for the delivery clinical trials depends on design and appropriate recruitment participants. Polygenic scores (PRS) show potential identifying at (AD). Our study comprehensively examines AD PRS utility using various methods models. Methods We compared prediction accuracy in ADNI ( N = 568) BioFINDER 766) cohorts five modelling approaches, three derivation methods, two genome-wide association...
A neuroimaging-based biomarker termed the brain age is thought to reflect variability in brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed examine potential drivers correlates of age.
Schizophrenia is a highly heritable disorder. Genome-wide association studies based largely on common alleles have identified over 100 schizophrenia risk loci, but it also evident from of copy number variants (CNVs) and exome-sequencing that rare are involved. Full characterization the contribution to disorder awaits deployment sequencing technology in very large sample sizes, meanwhile, as an interim measure, exome arrays allow non-synonymous be sampled at fraction cost. In analysis array...
Insomnia, hypersomnia, and an evening chronotype are common in individuals with bipolar disorder (BD), but whether this reflects shared genetic liability is unclear. Stratifying by BD subtypes could elucidate association inform sleep research.To assess polygenic risk scores (PRSs) for traits associated I II.This case-control study was conducted the United Kingdom Sweden participants control participants. Multinomial regression used to PRSs insomnia, daytime sleepiness, duration, compared...
Alzheimer's disease (AD) is a devastating neurodegenerative condition with significant genetic heritability. Several genes have been implicated in the onset of AD apolipoprotein E (APOE) gene being strongest single risk loci. Evidence suggests that effect APOE alters age during progression. Here, we aim to investigate impact and other variants outside region on younger older participants. Using data from both Disease Neuroimaging Initiative UK Biobank, computed polygenic score each...
Increasing evidence supports a role for deficient Wnt signaling in Alzheimer’s disease (AD). Studies reveal that the secreted antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques AD patients. Here, we investigate contribution of DKK3 synapse integrity healthy and brains. Our findings show expression is upregulated brains subjects protein levels increase at early stages disease. In hAPP-J20 hAPP NL-G-F/NL-G-F mouse models, extracellular are increased accumulates dystrophic neuronal...
The APOE-ε4 allele is known to predispose amyloid deposition and consequently strongly associated with Alzheimer's disease (AD) risk. There debate as whether the APOE gene accounts for all genetic variation of locus. Another question which remains carriers have other factors influencing progression positive individuals AD. We conducted a genome-wide association study in sample 5,390 homozygous (ε4ε4) (288 cases 5102 controls) aged 65 or over UK Biobank. found no significant associations SNPs...
Abstract Defining the mechanisms involved in aetiology of Alzheimer’s disease from genome-wide association studies alone is challenging since polygenic and most genetic variants are non-coding. Non-coding risk can influence gene expression by affecting miRNA binding those located within enhancers CTCF sites may through alterations chromatin states. In addition, their function be cell-type specific. They specifically microglial thus brain. Hence, transcriptome-wide have been applied to test...
Abstract Background Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan. Previous work only examined the of metformin over periods less than ten years, which may not be long enough capture true effect this on longevity. Methods We searched medical records Wales, UK, using Secure Anonymised Information Linkage dataset diabetes patients treated with (N = 129,140) and sulphonylurea 68,563). Non-diabetic controls...
Radiative transfer models predicting the bidirectional reflectance factor (BRF) of leaf canopies are powerful tools that relate biophysical parameters such as area index (LAI), fractional vegetation cover fV and fraction photosynthetically active radiation absorbed by green parts canopy (fAPAR) to remotely sensed data. One most successful approaches parameter estimation is inversion detailed radiative through construction Look-Up Tables (LUTs). The solution inverse problem requires...
Late onset Alzheimer’s disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim current study to identify novel genes associated with using largest up-to-date reference single nucleotide polymorphism (SNP) panel, accurate imputation software and a gene-based analysis approach tests patterns association within genes, in powerful genome-wide dataset International Genomics Project Consortium, comprising over 7 million genotypes from 17,008...
Abstract Polygenic risk scores (PRS) have been widely adopted as a tool for measuring common variant liability and they shown to predict lifetime of Alzheimer’s disease (AD) development. However, the relationship between PRS AD pathogenesis is largely unknown. To this end, we performed differential gene-expression associated disrupted biological pathway analyses vs. case/controls in human brain-derived cohort sample (cerebellum/temporal cortex; MayoRNAseq). The results highlighted already...
Polygenic risk scores (PRSs) can boost prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought resilience-conferring common variants (1) unaffected individuals having high PRSs for LOAD, and (2) APOE-ε4 carriers also LOAD. We used genome-wide association study (GWAS) contrast "resilient" at the highest LOAD with cases comparable risk. From GWAS results, constructed polygenic...
Abstract Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, carry increased burden deleterious mutations. At genome-wide level, our results implicate non-synonymous, splice site as well stop-altering single-nucleotide variations occurring at minor allele frequency ≥0.01% population. In independent replication sample 5,585 8,103 controls...