Biology subjects

Green, M. J.

Publications and source records attributed to Green, M. J..

6 recordsLinked to original sources

bioRxiv2025

Neuroanatomical Correlates of Negative Symptoms in Schizophrenia

BackgroundSchizophrenia is characterized by widespread structural brain abnormalities, but associations between structural abnormalities and negative symptom severity are not well understood. Negative symptoms have been conceptualized in a hierarchical structure of two second-order dimensions--motivation and pleasure (MAP) and expression (EXP)--and five first-order domains: anhedonia, avolition, and asociality (MAP), and blunted affect and alogia (EXP). A better understanding of the neural circuitry underlying negative symptom dimensions and domains is important given their reported association with poor functional outcome and lack of available treatments. Study DesignThe meta-analysis included 1,591 individuals with schizophrenia across 16 samples with structural imaging and Scale for Assessment of Negative Symptoms data. The study generated correlations of cortical thickness and subcortical volumes with the negative symptom dimensions and domains. Study resultsNegative symptoms showed mainly negative associations with cortical thickness and subcortical volumes. The effect sizes were small but there was a pattern of associations in predominantly frontal lobe cortical thickness and limbic subcortical volumes. The regional correlation patterns of cortical thickness and subcortical volumes with symptom domains support the conceptualized hierarchical structure of negative symptoms: correlations of MAP domains were stronger with the MAP than EXP dimension, and vice versa. Exploratory analyses with receptor densities further supported the hierarchy. ConclusionOur findings reveal small but consistent associations between negative symptom dimensions and predominantly prefrontal region cortical thickness, and limbic region volumes. These findings advance our understanding of the network of anatomical regions that may contribute to the severity of negative symptoms in schizophrenia.

neuroscience↗

bioRxiv2025

Genomic and morphological characterisation of a novel iridovirus, bivalve iridovirus 1 (BiIV1), infecting the common cockle (Cerastoderma edule)

1High rates of mortality of the common cockle, Cerastoderma edule, have occurred in the Wash Estuary, UK since 2008. A previous study linked the mortalities to a novel genotype of Marteilia cocosarum, with a strong correlation between cockle moribundity and the presence of M. cocosarum. Here, we characterise a novel iridovirus, identified by chance during metagenomic sequencing of a gradient purification of Marteilia cells, with presence also correlated to cockle moribundity. The novel 179,695 bp iridovirus, bivalve iridovirus 1 (BiIV1), encodes 193 predicted open reading frames and has a 41% G+C content. BiIV1 clusters together with other aquatic invertebrate iridoviruses in phylogenetic analyses and has a similar genome size to other invertebrate iridoviruses. Comparative analysis revealed that BiIV1 has lost three genes that were previously thought to be common amongst all iridoviruses but has also gained genes, potentially from horizontal transfer from its bivalve mollusc host(s). Electron microscopy showed 158 nm icosahedral virions present in the haemocytes of cockles, typical of those observed in host tissues infected with viruses of the family Iridoviridae. Prevalence of BiIV1 in moribund cockles was higher than that in apparently healthy cockles at most sites in the Wash Estuary, with up to 100% PCR prevalence in moribund cockles. Our findings provide the first genome for a bivalve-infecting iridovirus and identify a second bivalve-associated iridovirus in publicly available genomic datasets, adding to the knowledge of invertebrate iridovirus genomics and diversity.

molecular biology↗

bioRxiv2025

Characterisation of Marteilia cocosarum in the Wash Estuary, UK, linked to mass mortalities of cockles (Cerastoderma edule), and its relationship to closely related species

Globally, Marteilia parasites have been associated with significant mass mortality events in populations of commercially important bivalve molluscs, frequently resulting in large-scale fishery collapses and substantial socio-economic impacts. The Wash Estuary, UK, supports several bivalve fisheries, and among these, common cockles Cerastoderma edule have suffered unusually high mortalities since 2008. We investigate potential causes of these mortalities, and confirm infection with Marteilia cocosarum, strongly associated with cockle moribundity, also confirming its presence in archived samples collected in 2009. Molecular and light microscopy screening of samples collected during mortality events in 2021, including healthy (buried) and moribund (weak, unable to bury) cockles, indicated high prevalence of M. cocosarum in moribund cockles (PCR incidence up to 95%) in contrast to healthy cockles (up to 42%), suggesting an association between cockle moribundity and Marteilia infection. Analysis of the full ribosomal RNA array identified consistently different nucleotides between M. cocosarum infections in The Wash (denoted as genotype WE) and those in Wales (denoted genotype BI). 83% of infections in The Wash could be identified as M. cocosarum WE and 12% as M. cocosarum BI, with both genotypes recovered from 5% of infected animals. Histopathologically, M. cocosarum WE infects the gill, mantle and connective tissues, identical to observations of M. cocosarum infecting Welsh cockles. Ongoing cockle mortalities in The Wash raise concerns regarding the sustainability of this resource ecologically and economically. Additional measures may be required to reduce the spread of this pathogen, noting that its distribution beyond The Wash and Wales is currently unknown.

molecular biology↗

bioRxiv2019

Pharmacological enrichment of polygenic risk for precision medicine in complex disorders

Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to be directly informative for clinical interventions. We therefore sought to develop a framework to quantify an individuals common variant enrichment in clinically actionable systems responsive to existing drugs. This was achieved with a metric designated the pharmagenic enrichment score (PES), which we demonstrate for individual SNP profiles in a cohort of cases with schizophrenia. A large proportion of these had elevated PES in one or more of eight clinically actionable gene-sets enriched with schizophrenia associated common variation. Notable candidates targeting these pathways included vitamins, insulin modulating agents, and protein kinase inhibitors with putative neuroprotective properties. Interestingly, elevated PES was also observed in individuals with otherwise low common variant burden. The biological saliency of PES profiles were observed directly through their impact on gene expression in a subset of the cohort with matched transcriptomic data, supporting our assertion that this framework can integrate an individuals common variant risk to inform personalised interventions, including drug repositioning, for complex disorders such as schizophrenia.

genetics↗

bioRxiv2019

Derivation of Poly-Methylomic Profile Scores for Schizophrenia

Schizophrenia (SZ) and bipolar disorder (BD) share numerous clinical and biological features as well as environmental risk factors that may be associated with altered DNA methylation. In this study we sought to construct a Poly-Methylomic Profile Score (PMPS) for SZ, representing the degree of epigenome-wide methylation according to previously published findings; we then examined its association with SZ and BD in an independent sample. DNA methylation for 57 SZ, 59 BD cases and 55 healthy controls (HCs) was quantified using the Illumina 450K methylation beadchip. We constructed five PMPSs for different p-value thresholds using summary statistics reported in a large epigenome-wide schizophrenia case-control association study, weighted by individual CpG effect sizes. All SZ PMPSs were significantly elevated in SZ cases relative to HCs, with the score calculated at the most stringent threshold accounting for the greatest amount of variance in SZ (compared to other PMPSs derived at more inclusive p-value thresholds). However, none of the PMPSs were associated with BD, or a combined cohort of BD and SZ cases relative to HCs. Results demonstrating elevated PMPSs in SZ relative to BD did not survive correction for multiple testing. PMPSs were also not associated with positive or negative symptom severity. That this SZ-derived PMPSs was elevated among SZ, but not BD participants, suggests that epigenome-wide methylation patterns associated with schizophrenia may represent distinct pathophysiology that is yet to be elucidated. Whether this PMPS may be associated with neuroanatomical or other biological endophenotypes relevant to SZ and/or BD remains to be determined.

genetics↗

bioRxiv2018

The Medical Genome Reference Bank: Whole genomes and phenotype of 2,570 healthy elderly

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2,570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analysed the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. Individuals in the MGRB had fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK BioBank cohorts, consistent with risk depletion. Pervasive age-related somatic changes were correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. This research has been conducted using the UK Biobank Resource under Application Number 17984.

genomics↗