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Introduction
Additional affiliations
April 2015 - January 2021
Murdoch University
Position
- Lecturer
July 2013 - March 2015
January 2006 - July 2009
Publications
Publications (278)
Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here w...
Background:
In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases.
Objective:
In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI)...
Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify...
Background
Lifestyle modifications incorporating a healthy diet, physical activity, brain training and health monitoring have proven effective in preventing dementia and related cognitive decline (REF). The Australian‐Multidomain Lifestyle Intervention to reduce dementia risk (AU‐ARROW) is an ongoing 2‐yearintervention, which is the Australian cont...
The hippocampus exhibits volumetric differences between the left and right hemispheres (LHCV and RHCV) and asymmetry, yet the molecular mechanisms underlying these features remain unclear. In this study, we performed a meta-analysis of epigenome-wide association studies (EWAS) across six population-based cohorts (n=8,156; 53% women; mean age: 60.7...
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898...
Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, w...
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ t...
INTRODUCTION
The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World‐Wide FINGERS (WW‐FINGERS). As part of WW‐FINGERS, the Australian AU‐ARROW study mirrors aspects of FINGER, as well as US‐POINTER.
METHOD
AU‐ARROW is a randomized, single‐blind, multisite, 2‐year clinical trial ( n = 600; aged...
Camera trap model and setup choice can significantly affect data collection. This study investigated standard-angle Reconyx and wide-angle Swift camera traps in different setups and how the choice of equipment influenced detection and individual identification of the chuditch (Dasyurus geoffroii). Camera models were placed side-by-side in four setu...
Background
Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia.
Methods
We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delaye...
Despite the promising antitumor activity of SHP2 inhibitors in RAS-dependent tumours, overall responses have been limited by their narrow therapeutic window. Like with all MAPK pathway inhibitors, this is likely the result of compensatory pathway activation mechanisms. However, the underlying mechanisms of resistance to SHP2 inhibition remain unkno...
The use of anthropogenic resources is becoming increasingly common as species adapt to human‐induced environmental changes, but their use can expose species to new risks. Understanding how animals exploit these resources is important for guiding conservation management, particularly where species are threatened. The introduction of canola cropping...
Background:
The 1q21.1 distal and 15q11.2 BP1-BP2 CNVs exhibit regional and global brain differences compared to non-carriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intra-individual variability measures can be used to test for regional differences beyond global diffe...
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of gene expression from peripheral blood in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (7...
Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk...
Background:
Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility.
Methods:
We evaluated plasma, serum, and cerebrospin...
Background
Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging are markers of cerebral small vessel disease (cSVD), a major risk factor for Alzheimer’s disease and related dementia (ADRD). Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architectu...
Recently, Vibrio anguillarum, a Gram-negative pathogenic bacterium, has been becoming a major constraint on the development of the turbot aquaculture industry because of its characteristics of worldwide distribution, broad host range and potentially devastating impacts. Although the function of protein-coding mRNAs in the immune response against ba...
Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type- or condition-specific IR regulati...
Long noncoding RNAs (lncRNAs), can regulate mRNA by targeting miRNA in a competing endogenous RNA network, have become a hot topic in the research of fish immune mechanism recent years. While in turbot (Scophthalmus maximus L.), an economically important marine fish, there are limited researches into the role of lncRNAs in its immune response to ba...
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1,...
Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELP...
Diving behaviour of ‘surfacers' such as sea snakes, cetaceans and turtles is complex and multi-dimensional, thus may be better captured by multi-sensor biologging data. However, analysing these large multi-faceted datasets remains challenging, though a high priority. We used high-resolution multi-sensor biologging data to provide the first detailed...
Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA meth...
Polygenic risk scores (PRSs) can boost risk 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 to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-...
Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal...
Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal...
Polygenic risk scores (PRSs) can boost risk-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 to identify resilience-conferring common genetic variants in 1) unaffected individuals having high PRSs for LOAD, and 2) unaffected APOE -...
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we ai...
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 ris...
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...
Background
Previous findings for the genetic and environmental contributions to DNA methylation variation were for limited age ranges only. We investigated the lifespan contributions and their implications for human health for the first time.
Methods
1,720 monozygotic twin (MZ) pairs and 1,107 dizygotic twin (DZ) pairs aged 0-92 years were include...
The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has...
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study res...
Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient’s response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from...
Perivascular space burden (PVS) is an emerging and possibly the earliest magnetic resonance imaging (MRI)-marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Its molecular underpinnings are unknown. Genome-wide and whole-exome association studies in 40,095 participants (21 population-based cohorts, 66.3±8.6 years...
Introduction:
This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).
Methods:
Plasma proteins were measured using Simoa...
DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq...
DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neur...
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study res...
Very preterm infants (≤ 32 weeks gestational age; GA) are at high risk of developing late‐onset sepsis (LOS; onset after 72 hours of age), which is associated with increased mortality and short‐ and long‐term morbidity. The early symptoms of suspected LOS are non‐specific and are managed with empiric broad‐spectrum antibiotics, with well‐documented...
Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour...
Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically c...
Background
People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and th...
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain st...
Context: Determining the most efficient detection method for a target species is key for successful wildlife monitoring
and management. Driven transects and sign surveys are commonly used to monitor populations of the endangered numbat
(Myrmecobius fasciatus). Camera trapping is being explored as a new method. These methods were unevaluated for
eff...
When using camera traps for wildlife studies, determining suitable camera models and deployment methods is
essential for achieving study objectives. We aimed to determine if camera trap performance can be increased by (1) using
cameras with wider detection angles, and (2) by periodically repositioning cameras within sites. We compared three
camera...
The Enhancing NeuroImaging Genetics through Meta‐Analysis copy number variant (ENIGMA‐CNV) and 22q11.2 Deletion Syndrome Working Groups (22q‐ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA‐CNV WG has...
Background
The phenomenon of widespread and dynamic intron retention (IR) programs in cells of vertebrate species has recently gained increasing attention. It has been shown that IR is involved in a multitude of cell-physiological processes, while aberrant IR profiles have been associated with numerous human diseases including several cancers.
Gap...
Dynamic Body Acceleration (DBA), measured through animal-attached tags, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. Following respirometry to calibrate oxygen consumption rate ( M O 2 ) with DBA under controlled conditions, predictive models can be applied to DBA data collected from free-rangin...
Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (G...
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain str...
The Enhancing Neuroimaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has...
Epigenetics plays a profound role in normal cellular processes, and alterations to normal epigenetic processes lead to phenotypic plasticity and disease progression, prompting widespread interest in understanding the interactions between the epigenome, the genome, and the environment. As such, epigenetic profiling in twins affords the opportunity t...
Background
DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan.
Results
In...
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were...
The estimation of the time since death (minimum Post Mortem Interval, minPMI) is an essential aspect of forensic investigations. This is particularly complex when a human body is found submerged, floating or beached in a marine environment. When a cadaver is found in a terrestrial environment the minPMI estimation is generally based on the presence...
DNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer...
Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer's disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases...
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individua...
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individua...
Life history, reproduction, and survival are fundamentally linked to energy expenditure and acquisition. Dynamic Body Acceleration (DBA), measured through animal-attached data-loggers or transmitters, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. After using respirometry to calibrate oxygen consu...
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins...
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins...