A5080731301- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Genomics and Rare Diseases
- Retinoids in leukemia and cellular processes
- Bioinformatics and Genomic Networks
- Eating Disorders and Behaviors
- Genomic variations and chromosomal abnormalities
- MicroRNA in disease regulation
- Systemic Lupus Erythematosus Research
- Nutrition, Genetics, and Disease
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Functional Brain Connectivity Studies
- RNA modifications and cancer
- Tryptophan and brain disorders
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Diet and metabolism studies
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Schizophrenia research and treatment
- Mental Health Treatment and Access
- Obesity, Physical Activity, Diet
- Vitamin D Research Studies
University of Tasmania
2024-2025
University of Newcastle Australia
2018-2024
Hunter Medical Research Institute
2019-2024
Menzies Institute for Medical Research
2024
The University of Melbourne
2023
There is a long-standing interest in exploring the relationship between blood-based biomarkers and psychiatric disorders, despite their causal role being difficult to resolve observational studies. In this study, we leverage genome-wide association study data for large panel of heritable serum biochemical traits refine our understanding effect biochemical-psychiatric trait pairings. We observed widespread positive negative genetic correlation disorders traits. Causal inference was then...
Abstract Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) in schizophrenia relates interregional variation distinct neural cell types, as inferred from established gene expression data person-specific genomic variation. This study comprised 1849 participants total, including a discovery (140 cases 1267 controls) validation...
Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform largest genome-wide association study (GWAS) of retinol to date up 22,274 participants. We identify eight common variant loci associated with retinol, as well rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside main transport complex (RBP4:TTR) related lipid biology, energy homoeostasis, and...
While RNA expression appears to be altered in several brain disorders, the constraints of postmortem analysis make it impractical for well-powered population studies and biomarker development. Given that unique molecular composition neurons are reflected their extracellular vesicles (EVs), we hypothesized fractionation neuron derived EVs provides an opportunity specifically profile encapsulated contents noninvasively from blood. To investigate this hypothesis, determined miRNA microtubule...
Retinoid metabolites of vitamin A are intrinsically linked to neural development, connectivity and plasticity, have been implicated in the pathophysiology schizophrenia. We hypothesised that a greater burden common rare genomic variation genes involved with retinoid biogenesis signalling could be associated schizophrenia its cognitive symptoms. Common variants largest genome-wide association study were aggregated used formulate polygenic risk score (PRS
Abstract Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to directly informative for clinical interventions. We therefore sought develop framework quantify an individual’s variant enrichment in clinically actionable systems responsive existing drugs. This was achieved metric designated pharmagenic (PES), which we demonstrate...
BackgroundUnpacking molecular perturbations associated with features of schizophrenia is a critical step towards understanding phenotypic heterogeneity in the disorder. Recent epigenome-wide association studies (EWAS) have uncovered pervasive dysregulation DNA methylation schizophrenia, however, clinical disorder which account for large proportion variability remain relatively underexplored.MethodsWe comprehensively analysed patterns cohort 381 individuals from deeply phenotyped Australian...
BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach lower blood pressure (BP) not equally across all BP heritable, and genetics may be useful tool overcome treatment response heterogeneity. We investigated whether the of could used identify individuals with hypertension who receive particular benefit from lowering sodium intake boosting potassium levels....
Genetically informed drug development and repurposing is an attractive prospect for improving patient outcomes in psychiatry; however, the effectiveness of these endeavors confounded by heterogeneity. We propose approach that links interventions implicated disorder-associated genetic risk, at population level, to a framework can target compounds individuals. Specifically, results from genome-wide association studies are integrated with expression data prioritize individual "directional...
Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology psychiatric illness. This may be attractive target for clinical intervention as glycaemia can modulated by both lifestyle factors and pharmacological agents. However, are inherently confounded, therefore, causal relationships cannot reliably established. We employed genetic variants rigorously associated with three traits (fasting glucose, fasting insulin, glycated...
Measures of lung function are heritable, and thus, we sought to utilise genetics propose drug-repurposing candidates that could improve respiratory outcomes. Lung measures were found be genetically correlated with seven druggable biochemical traits, further evidence a causal relationship between increased fasting glucose diminished function. Moreover, developed polygenic scores for specifically within pathways known drug targets investigated their pulmonary phenotypes gene expression in...
Abstract Background Anorexia nervosa (AN) is a psychiatric disorder associated with marked morbidity. Whilst AN genetic studies could identify novel treatment targets, integration of functional genomics data, including transcriptomics and proteomics, would assist to disentangle correlated signals reveal causally genes. Methods We used models genetically imputed expression splicing from 14 tissues, leveraging mRNA, protein, mRNA alternative weights genes, proteins, transcripts, respectively,...
Abstract Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex. Recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in many psychiatric which could be mediated by changes cerebral Here, we leveraged publicly available genome-wide association study data to explore shared architecture for relationships between panel of 50 measures cortical thickness surface area. Linkage...
Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications microRNA's expression encompassed by common haplotype tagged rs1625579, likely be others, such as variable number tandem repeat (VNTR) variant rs58335419, that no proxy on SNP genotyping platforms used GWAS date. Using whole-genome sequencing data from patients (n...
Psychiatric disorders have a polygenic architecture, often associated with dozens or hundreds of independent genomic loci. Most loci impact noncoding regions the genome, suggesting that majority disease heritability originates from disruption regulatory sequences. While most research has focused on variants modify DNA elements, those affecting cis-acting RNA sequences, such as miRNA binding sites, are also likely to significant impact. We intersected genome-wide association study (GWAS)...
Blood pressure (BP) is influenced by both genetics and diet. Dietary management of hypertension includes increasing potassium-rich foods while reducing sodium intakes. potassium intakes can be measured objectively using urinary potassium, with lower to ratios associated BP (1) . Understanding the interplay between diet may useful in treating determining which individuals receive an outsized benefit from lowering their ratio. This study aims investigate whether identifying genetic risk for...