ORCID Profile
0000-0003-1684-3750
Current Organisations
CSIRO
,
The University of Texas Health Science Center at San Antonio Graduate School of Biomedical Sciences
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Publisher: IEEE
Date: 08-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 30-09-2022
DOI: 10.1038/S41586-022-05165-3
Abstract: Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control in iduals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control in iduals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated ( P 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN ) and variants (such as at GRK5 and NOS3 ). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Publisher: JMIR Publications Inc.
Date: 24-01-2022
DOI: 10.2196/31970
Abstract: An aging population, accompanied by the prevalence of age-related diseases, presents a significant burden to health systems. This is exacerbated by an increasing shortage of aged care staff due to the existing workforce entering their retirement and fewer young people being attracted to work in aged care. In line with consumer preferences and potential cost-efficiencies, government and aged care providers are increasingly seeking options to move care and support to the community or home as opposed to residential care facilities. However, compared to residential care, home environments may provide limited opportunity for monitoring patients’ progression/decline in functioning and therefore limited opportunity to provide timely intervention. To address this, the Smarter Safer Homes (SSH) platform was designed to enable self-monitoring and/or management, and to provide aged care providers with support to deliver their services. The platform uses open Internet of Things communication protocols to easily incorporate commercially available sensors into the system. Our research aims to detail the benefits of utilizing the SSH platform as a service in its own right as well as a complementary service to more traditional/historical service offerings in aged care. This work is anticipated to validate the capacity and benefits of the SSH platform to enable older people to self-manage and aged care service providers to support their clients to live functionally and independently in their own homes for as long as possible. This study was designed as a single-blinded, stratified, 12-month randomized controlled trial with participants recruited from three aged care providers in Queensland, Australia. The study aimed to recruit 200 people, including 145 people from metropolitan areas and 55 from regional areas. Participants were randomized to the intervention group (having the SSH platform installed in their homes to assist age care service providers in monitoring and providing timely support) and the control group (receiving their usual aged care services from providers). Data on community care, health and social-related quality of life, health service utilization, caregiver burden, and user experience of both groups were collected at the start, middle (6 months), and end of the trial (12 months). The trial recruited its first participant in April 2019 and data collection of the last participant was completed in November 2020. The trial eventually recruited 195 participants, with 98 participants allocated to the intervention group and 97 participants allocated to the control group. The study also received participants’ health service data from government data resources in June 2021. A crisis is looming to support the aging population. Digital solutions such as the SSH platform have the potential to address this crisis and support aged care in the home and community. The outcomes of this study could improve and support the delivery of aged care services and provide better quality of life to older Australians in various geographical locations. Australian New Zealand Clinical Trials Registry ACTRN12618000829213 n6a75em DERR1-10.2196/31970
Publisher: Springer Science and Business Media LLC
Date: 14-11-2022
Publisher: Springer Science and Business Media LLC
Date: 03-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-01-2019
DOI: 10.1212/WNL.0000000000006851
Abstract: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 −8 and LINC00539/ZDHHC20, p = 5.82 × 10 −9 . Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up s le or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( p value for BI, p [BI] = 9.38 × 10 −25 p [SSBI] = 5.23 × 10 −14 for hypertension), smoking ( p [BI] = 4.4 × 10 −10 p [SSBI] = 1.2 × 10 −4 ), diabetes ( p [BI] = 1.7 × 10 −8 p [SSBI] = 2.8 × 10 −3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 −18 p [SSBI] = 2.3 × 10 −7 ), stroke ( p [BI] = 3.9 × 10 −69 p [SSBI] = 3.2 × 10 −24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 −157 p [SSBI] = 3.16 × 10 −106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( p ≤ 0.0022), without indication of directional pleiotropy. In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2018
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2017
Publisher: Cold Spring Harbor Laboratory
Date: 17-08-2017
DOI: 10.1101/176511
Abstract: General cognitive function is a prominent human trait associated with many important life outcomes 1,2 , including longevity 3 . The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants 4,5,6 . Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360 age range = 16 to 102). We found 9,714 genome-wide significant SNPs ( P x 10 −8 ) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ , ATXN1 , MAPT , AUTS2 , and P2RY6 . Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent s les. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
DOI: 10.1038/S41467-018-04362-X
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486 age 16–102) and find 148 genome-wide significant independent loci ( P 5 × 10 −8 ) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent s les. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Publisher: IEEE
Date: 08-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2016
Publisher: Research Square Platform LLC
Date: 04-01-2022
DOI: 10.21203/RS.3.RS-1175817/V1
Abstract: Previous genome-wide association studies (GWAS) of stroke, the second leading cause of death, have been conducted in populations of predominantly European ancestry.1,2 We undertook cross-ancestry GWAS meta-analyses of stroke and its subtypes in 110,182 stroke patients (33% non-European) and 1,503,898 control in iduals of five ancestries from population- and clinic-based studies, nearly doubling the number of cases in previous stroke GWAS. We identified association signals at 89 independent loci, of which 61 were novel. Effect sizes were overall highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis using a novel machine-learning approach,3 transcriptome and proteome-wide association analyses revealed putative causal genes (e.g. SH3PXD2A and FURIN) and variants (e.g. at GRK5 and NOS3). Using a novel three-pronged approach,4 we provided genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWAS with vascular risk factor GWAS (iPGS) showed strong prediction of ischemic stroke risk in European and, for the first time, East-Asian populations.5,6 The iPGS performed better than stroke PGS alone and better than previous best iPGS, in Europeans and East-Asians. Transferability of European-specific iPGS to East-Asians was limited. Stroke genetic risk scores were predictive of ischemic stroke independent of clinical risk factors in 52,600 clinical trial participants with cardiometabolic disease and performed considerably better than previous scores, both in Europeans and East-Asians. Altogether our results provide critical insight to inform biology, reveal potential drug targets for intervention, and provide genetic risk prediction tools across ancestries for targeted prevention.
Publisher: Springer Science and Business Media LLC
Date: 17-09-2018
Publisher: JMIR Publications Inc.
Date: 11-08-2021
DOI: 10.2196/27047
Abstract: As life expectancy grows, so do the challenges of caring for an aging population. Older adults, including people with dementia, want to live independently and feel in control of their lives for as long as possible. Assistive technologies powered by artificial intelligence and internet of things devices are being proposed to provide living environments that support the users’ safety, psychological, and medical needs through remote monitoring and interventions. This study investigates the functional, psychosocial, and environmental needs of people living with dementia, their caregivers, clinicians, and health and social care service providers toward the design and implementation of smart home systems. We used an iterative user-centered design approach comprising 9 substudies. First, semistructured interviews (9 people with dementia, 9 caregivers, and 10 academic and clinical staff) and workshops (35 pairs of people with dementia and caregivers, and 12 health and social care clinicians) were conducted to define the needs of people with dementia, home caregivers, and professional stakeholders in both daily activities and technology-specific interactions. Then, the spectrum of needs identified was represented via patient–caregiver personas and discussed with stakeholders in a workshop (14 occupational therapists 4 National Health Service pathway directors and 6 researchers in occupational therapy, neuropsychiatry, and engineering) and 2 focus groups with managers of health care services (n=8), eliciting opportunities for innovative care technologies and public health strategies. Finally, these design opportunities were discussed in semistructured interviews with participants of a smart home trial involving environmental sensors, physiological measurement devices, smartwatches, and tablet-based chatbots and cognitive assessment puzzles (10 caregivers and 2 people with dementia). A thematic analysis revealed factors that motivate household members to use these technologies. Outcomes of these activities include a qualitative and quantitative analysis of patient, caregiver, and clinician needs and the identification of challenges and opportunities for the design and implementation of remote monitoring systems in public health pathways. Participatory design methods supported the triangulation of stakeholder perspectives to aid the development of more patient-centered interventions and their translation to clinical practice and public health strategy. We discuss the implications and limitations of our findings, the value and the applicability of our methodology, and directions for future research.
Publisher: MDPI AG
Date: 16-12-2022
DOI: 10.3390/S22249944
Abstract: Social isolation (SI) and loneliness are ‘invisible enemies’. They affect older people’s health and quality of life and have significant impact on aged care resources. While in-person screening tools for SI and loneliness exist, staff shortages and psycho-social challenges fed by stereotypes are significant barriers to their implementation in routine care. Autonomous sensor-based approaches can be used to overcome these challenges by enabling unobtrusive and privacy-preserving assessments of SI and loneliness. This paper presents a comprehensive overview of sensor-based tools to assess social isolation and loneliness through a structured critical review of the relevant literature. The aim of this survey is to identify, categorise, and synthesise studies in which sensing technologies have been used to measure activity and behavioural markers of SI and loneliness in older adults. This survey identified a number of feasibility studies using ambient sensors for measuring SI and loneliness activity markers. Time spent out of home and time spent in different parts of the home were found to show strong associations with SI and loneliness scores derived from standard instruments. This survey found a lack of long-term, in-depth studies in this area with older populations. Specifically, research gaps on the use of wearable and smart phone sensors in this population were identified, including the need for co-design that is important for effective adoption and practical implementation of sensor-based SI and loneliness assessment in older adults.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
DOI: 10.1038/S41467-018-07340-5
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 in iduals for cIMT, and 48,434 in iduals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4 . LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Publisher: JMIR Publications Inc.
Date: 31-08-2021
Abstract: n aging population, accompanied by the prevalence of age-related diseases, presents a significant burden to health systems. This is exacerbated by an increasing shortage of aged care staff due to the existing workforce entering their retirement and fewer young people being attracted to work in aged care. In line with consumer preferences and potential cost-efficiencies, government and aged care providers are increasingly seeking options to move care and support to the community or home as opposed to residential care facilities. However, compared to residential care, home environments may provide limited opportunity for monitoring patients’ progression/decline in functioning and therefore limited opportunity to provide timely intervention. To address this, the Smarter Safer Homes (SSH) platform was designed to enable self-monitoring and/or management, and to provide aged care providers with support to deliver their services. The platform uses open Internet of Things communication protocols to easily incorporate commercially available sensors into the system. ur research aims to detail the benefits of utilizing the SSH platform as a service in its own right as well as a complementary service to more traditional/historical service offerings in aged care. This work is anticipated to validate the capacity and benefits of the SSH platform to enable older people to self-manage and aged care service providers to support their clients to live functionally and independently in their own homes for as long as possible. his study was designed as a single-blinded, stratified, 12-month randomized controlled trial with participants recruited from three aged care providers in Queensland, Australia. The study aimed to recruit 200 people, including 145 people from metropolitan areas and 55 from regional areas. Participants were randomized to the intervention group (having the SSH platform installed in their homes to assist age care service providers in monitoring and providing timely support) and the control group (receiving their usual aged care services from providers). Data on community care, health and social-related quality of life, health service utilization, caregiver burden, and user experience of both groups were collected at the start, middle (6 months), and end of the trial (12 months). he trial recruited its first participant in April 2019 and data collection of the last participant was completed in November 2020. The trial eventually recruited 195 participants, with 98 participants allocated to the intervention group and 97 participants allocated to the control group. The study also received participants’ health service data from government data resources in June 2021. crisis is looming to support the aging population. Digital solutions such as the SSH platform have the potential to address this crisis and support aged care in the home and community. The outcomes of this study could improve and support the delivery of aged care services and provide better quality of life to older Australians in various geographical locations. ustralian New Zealand Clinical Trials Registry ACTRN12618000829213 n6a75em ERR1-10.2196/31970
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2018
Publisher: Cold Spring Harbor Laboratory
Date: 11-10-2017
DOI: 10.1101/198234
Abstract: High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2018
DOI: 10.1038/S41588-018-0297-3
Abstract: In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2018
Publisher: Elsevier BV
Date: 06-2016
Publisher: Cold Spring Harbor Laboratory
Date: 28-08-2017
DOI: 10.1101/173831
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 in iduals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Muralidharan Sargurupremraj.