A5076142860- Attention Deficit Hyperactivity Disorder
- Alzheimer's disease research and treatments
- Bipolar Disorder and Treatment
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- Neurotransmitter Receptor Influence on Behavior
- Child and Adolescent Psychosocial and Emotional Development
- Intergenerational Family Dynamics and Caregiving
- Functional Brain Connectivity Studies
- RNA regulation and disease
- Diet and metabolism studies
- Tryptophan and brain disorders
- Genomics and Rare Diseases
- Folate and B Vitamins Research
- Biological Research and Disease Studies
- Parkinson's Disease Mechanisms and Treatments
- Neuroendocrine regulation and behavior
- Identity, Memory, and Therapy
- Genomics and Phylogenetic Studies
- Complement system in diseases
Nottingham Trent University
2020-2025
University of Nottingham
2015-2020
University of Manchester
2010-2018
Boston University
2018
Erasmus MC
2018
Framingham Heart Study
2018
The University of Texas Health Science Center at San Antonio
2018
Institute for Neurodegenerative Disorders
2018
Manchester Academic Health Science Centre
2018
Queen's Medical Centre
2016
Abstract Characterization of the genetic landscape Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for better understanding associated pathophysiological processes. We performed two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases 677,663 controls. found 75 risk loci, which 42 were new at time analysis. Pathway enrichment analyses confirmed involvement amyloid/tau pathways highlighted microglia implication. Gene...
Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) associated with in several studies, an average 1.2 odds ratio evidence of heterogeneity across data sets.To investigate sources by refining the DAT1 association using additional markers investigating gene-environment interaction between maternal use alcohol tobacco during...
Abstract Human DNA methylation data have been used to develop biomarkers of ageing, referred as ‘epigenetic clocks’, which widely identify differences between chronological age and biological in health disease including neurodegeneration, dementia other brain phenotypes. Existing clocks shown be highly accurate blood but are less precise when older samples or tissue types not included training the model, brain. We aimed a novel epigenetic clock that performs optimally human cortex has...
Abstract Genome-wide association studies of late-onset Alzheimer’s disease risk have previously identified genes primarily expressed in microglia that form a transcriptional network. Using transgenic mouse models amyloid deposition, we showed many the orthologues these are co-expressed and associated with pathology. In this new study, generate an improved RNA-seq-derived network is amyloid-responsive statistically compare gene-level variation previous human genome-wide to predict at least...
Abstract Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer’s disease, by its enrichment in transcriptional networks expressed microglia. However, function OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic disease and 1234 control individuals, confirm variant, rs1131454, is associated increased for disease. The same locus has been recently severe coronavirus 2019 (COVID-19) outcomes, linking both diseases....
Abstract Mild-cognitive impairment (MCI) occurs in up to one-fifth of individuals over the age 65, with approximately a third MCI converting dementia later life. There is growing necessity for early identification those at risk as pathological processes begin decades before onset symptoms. A cohort 122 diagnosed and followed 36-month period conversion late-onset Alzheimer’s disease (LOAD) were genotyped on NeuroChip array along pathologically confirmed cases LOAD cognitively normal controls....
ABSTRACT Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, the failure to find effective treatments suggests that underlying pathology remains poorly understood. Due its strong heritability, deciphering genetic landscape of AD related dementia (ADD) unique opportunity advance our knowledge. We completed meta-analysis genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases 401,577 controls) with most promising signals...
Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles tau in neocortex. We profiled DNA methylation two regions cortex from 631 donors, performing an epigenome-wide association study multiple measures AD neuropathology. meta-analyzed our results with those previous studies (total n = 2013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated pathology...
Background: A common polymorphism in the serotonin transporter gene ( SLC6A4 , 5HTT ) has been repeatedly shown to moderate influence of childhood adversity and stressful life events on development psychopathology. Using data from English Romanian Adoptee Study, a prospective‐longitudinal study individuals n = 125) exposed severe early institutional deprivation (ID), we tested whether effect ID adolescent emotional problems is moderated by genotype adolescence. Methods: Emotional were...
The primary purpose of this study was to confirm the association a specific haplotype dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source heterogeneity seen across published studies.The authors previously reported ADHD with subgroup chromosomes containing alleles two variable-number tandem repeat polymorphisms within 3' untranslated region intron 8 gene. They now report on in sample combined-type probands.The original observations were...
Abstract Attention deficit hyperactivity disorder (ADHD) is currently one of the most prevalent childhood behavioral disorders. The found to be highly heritable, suggesting a large genetic component. Association studies have repeatedly implicated dopamine transporter (DAT1) gene, and in particular 10‐repeat allele variable number tandem repeat (VNTR) polymorphism located 3′UTR gene. Inconclusive data has been generated from several earlier on functional effects this polymorphism. Therefore,...
Early institutional deprivation is a risk factor for Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. However not all individuals are affected. We tested the hypothesis that this heterogeneity influenced by gene x environment (GxE) interaction and genetic polymorphisms involved in dopamine neurotransmission moderate effects of severe early on symptoms ADHD (sADHD). Using prospective-longitudinal design sADHD were measured at ages 6, 11, 15 years sample who experienced (up to 42...
Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it important to understand how tau protein itself, pathways implicated its turnover, change during aging. We investigated age-related changes total phosphorylated brain samples from two cohorts of cognitively normal individuals spanning 19–74 years, without overt neurodegeneration. One cohort utilised resected tissue other used...
Abstract Attention deficit hyperactivity disorder (ADHD) is the most common behavioral affecting children worldwide. The male bias in prevalence of disorder, suggests that some susceptibility genes may lie on X chromosome. In this study we present evidence for a role X‐linked steroid sulfatase ( STS ) gene and neurosteroids development ADHD. Previously it has been observed probands with ADHD have lower serum concentrations DHEA, which synthesized from DHEA‐S by . further support, boys suffer...
Late-onset Alzheimer's disease (LOAD) accounts for 95% of all cases and is genetically complex in nature. Overlapping clinical neuropathological features between AD, FTD Parkinson's highlight the potential role genetic pleiotropy across diseases. Recent genome-wide association studies (GWASs) have uncovered 20 new loci AD risk; however, these exhibit small effect sizes. Using NGS, here we perform analyses using exome-wide candidate-gene-driven approaches.
Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations components of the Sonic Hedgehog (S HH) signaling cascade. Shh expressed dynamic, spatiotemporal domains within epithelial rugae and plays key role driving epithelial-mesenchymal interactions are central to development secondary palate. However, gene regulatory networks downstream (Hh) incompletely characterized. Here, we show ectopic Hh palatal mesenchyme disrupts oral-nasal...