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  1. Article ; Online: Can epigenetics shine a light on the biological pathways underlying major mental disorders?

    Alameda, Luis / Trotta, Giulia / Quigley, Harriet / Rodriguez, Victoria / Gadelrab, Romayne / Dwir, Daniella / Dempster, Emma / Wong, Chloe C Y / Forti, Marta Di

    Psychological medicine

    2022  Volume 52, Issue 9, Page(s) 1645–1665

    Abstract: A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset ... ...

    Abstract A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the development of novel pharmacological treatments. Epigenetic mechanisms have emerged as mediators of environmental and genetic risk factors which might play a role in disease onset, including childhood adversity (CA) and cannabis use (CU). Particularly, human research exploring DNA methylation has provided new and promising insights into the role of biological pathways implicated in the aetio-pathogenesis of psychiatric conditions, including: monoaminergic (Serotonin and Dopamine), GABAergic, glutamatergic, neurogenesis, inflammatory and immune response and oxidative stress. While these epigenetic changes have been often studied as disease-specific, similarly to the investigation of environmental risk factors, they are often transdiagnostic. Therefore, we aim to review the existing literature on DNA methylation from human studies of psychiatric diseases (i) to identify epigenetic modifications mapping onto biological pathways either transdiagnostically or specifically related to psychiatric diseases such as Eating Disorders, Post-traumatic Stress Disorder, Bipolar and Psychotic Disorder, Depression, Autism Spectrum Disorder and Anxiety Disorder, and (ii) to investigate a convergence between some of these epigenetic modifications and the exposure to known risk factors for psychiatric disorders such as CA and CU, as well as to other epigenetic confounders in psychiatry research.
    MeSH term(s) Autism Spectrum Disorder/genetics ; DNA Methylation/genetics ; Epigenesis, Genetic ; Humans ; Mental Disorders/genetics ; Psychotic Disorders/genetics ; Stress Disorders, Post-Traumatic/genetics
    Language English
    Publishing date 2022-02-23
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 217420-0
    ISSN 1469-8978 ; 0033-2917
    ISSN (online) 1469-8978
    ISSN 0033-2917
    DOI 10.1017/S0033291721005559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of hyperglycaemia on complications of COVID-19: A meta-analysis of observational studies.

    Lee, Ming H / Wong, Chloe / Ng, Cheng H / Yuen, David C W / Lim, Amanda Y L / Khoo, Chin M

    Diabetes, obesity & metabolism

    2020  Volume 23, Issue 1, Page(s) 287–289

    MeSH term(s) COVID-19 ; Humans ; Hyperglycemia ; Pandemics ; Prognosis ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-09-18
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 1454944-x
    ISSN 1463-1326 ; 1462-8902
    ISSN (online) 1463-1326
    ISSN 1462-8902
    DOI 10.1111/dom.14184
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neuronal Network Excitability in Alzheimer's Disease: The Puzzle of Similar versus Divergent Roles of Amyloid β and Tau.

    Kazim, Syed Faraz / Seo, Joon Ho / Bianchi, Riccardo / Larson, Chloe S / Sharma, Abhijeet / Wong, Robert K S / Gorbachev, Kirill Y / Pereira, Ana C

    eNeuro

    2021  Volume 8, Issue 2

    Abstract: Alzheimer's disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron ... ...

    Abstract Alzheimer's disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression, may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Aβ and tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy before the development of plaques. Similarly, pathologic accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.
    MeSH term(s) Aged ; Alzheimer Disease ; Amyloid beta-Peptides/metabolism ; Hippocampus/metabolism ; Humans ; Neurons/metabolism ; tau Proteins/metabolism
    Chemical Substances Amyloid beta-Peptides ; tau Proteins
    Language English
    Publishing date 2021-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0418-20.2020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Effects of hyperglycaemia on complications of COVID-19: A meta-analysis of observational studies

    Lee, Ming H / Wong, Chloe / Ng, Cheng H / Yuen, David C W / Lim, Amanda Y L / Khoo, Chin M

    Diabetes obes. metab

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #738387
    Database COVID19

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  5. Article: High Prevalence and Mechanism Associated With Extended Spectrum Beta-Lactamase-Positive Phenotype in

    Teng, Jade L L / Luo, Ruibang / Tang, Bone S F / Fong, Jordan Y H / Wang, Li / Jia, Lilong / Wong, Chloe K S / Chan, Elaine / Leung, Amy W S / Siu, Gilman K H / Chiu, Tsz-Ho / Fung, Ami M Y / Wu, Alan K L / Yeung, Man-Lung / Lau, Susanna K P / Woo, Patrick C Y

    Frontiers in microbiology

    2021  Volume 12, Page(s) 618894

    Abstract: In this study, we reported the prevalence and mechanism associated with the extended-spectrum beta-lactamase (ESBL)-positive phenotype ... ...

    Abstract In this study, we reported the prevalence and mechanism associated with the extended-spectrum beta-lactamase (ESBL)-positive phenotype in
    Language English
    Publishing date 2021-02-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.618894
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effects of hyperglycaemia on complications of COVID ‐19

    Lee, Ming H. / Wong, Chloe / Ng, Cheng H. / Yuen, David C. W. / Lim, Amanda Y. L. / Khoo, Chin M.

    Diabetes, Obesity and Metabolism ; ISSN 1462-8902 1463-1326

    A meta‐analysis of observational studies

    2020  

    Keywords Internal Medicine ; Endocrinology, Diabetes and Metabolism ; Endocrinology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    DOI 10.1111/dom.14184
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans.

    Roberts, Amy L / Morea, Alessandro / Amar, Ariella / Zito, Antonino / El-Sayed Moustafa, Julia S / Tomlinson, Max / Bowyer, Ruth C E / Zhang, Xinyuan / Christiansen, Colette / Costeira, Ricardo / Steves, Claire J / Mangino, Massimo / Bell, Jordana T / Wong, Chloe C Y / Vyse, Timothy J / Small, Kerrin S

    eLife

    2022  Volume 11

    Abstract: Background: Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally ... ...

    Abstract Background: Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown.
    Methods: We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis.
    Results: We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence.
    Conclusions: Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.
    Funding: KSS acknowledges funding from the Medical Research Council [MR/M004422/1 and MR/R023131/1]. JTB acknowledges funding from the ESRC [ES/N000404/1]. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London.
    MeSH term(s) Female ; Humans ; Male ; Cardiovascular Diseases/genetics ; Cross-Sectional Studies ; Follow-Up Studies ; Outcome Assessment, Health Care ; Prospective Studies ; X Chromosome Inactivation
    Language English
    Publishing date 2022-11-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Twin Study
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.78263
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation.

    Saffari, Ayden / Arno, Matt / Nasser, Eric / Ronald, Angelica / Wong, Chloe C Y / Schalkwyk, Leonard C / Mill, Jonathan / Dudbridge, Frank / Meaburn, Emma L

    Molecular autism

    2019  Volume 10, Page(s) 38

    Abstract: Background: A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins ... ...

    Abstract Background: A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC.
    Methods: Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (
    Results: In the discordant twin analysis, three genes showed evidence for DE at FDR < 10%:
    Limitations: Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis.
    Conclusions: Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals.
    MeSH term(s) Autistic Disorder/blood ; Autistic Disorder/genetics ; Autistic Disorder/immunology ; Case-Control Studies ; Cluster Analysis ; DNA Methylation/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Male ; Sequence Analysis, RNA ; Transcription, Genetic ; Twins, Monozygotic/genetics
    Language English
    Publishing date 2019-11-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2540930-X
    ISSN 2040-2392 ; 2040-2392
    ISSN (online) 2040-2392
    ISSN 2040-2392
    DOI 10.1186/s13229-019-0285-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism

    Gokul Ramaswami / Hyejung Won / Michael J. Gandal / Jillian Haney / Jerry C. Wang / Chloe C. Y. Wong / Wenjie Sun / Shyam Prabhakar / Jonathan Mill / Daniel H. Geschwind

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone ... ...

    Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone acetylation datasets from a collection of post mortem brain tissues and identify a convergent molecular subtype of ASD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism

    Gokul Ramaswami / Hyejung Won / Michael J. Gandal / Jillian Haney / Jerry C. Wang / Chloe C. Y. Wong / Wenjie Sun / Shyam Prabhakar / Jonathan Mill / Daniel H. Geschwind

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone ... ...

    Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone acetylation datasets from a collection of post mortem brain tissues and identify a convergent molecular subtype of ASD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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