72 research outputs found
A diverse array of genetic factors contribute to the pathogenesis of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation
frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life
threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease
are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and
chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and
generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated
genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number
variation have also been identified; and an effect of ethnicity on susceptibility has been described.http://dx.doi.org/10.1186/1750-1172-8-2IS
Linking genes to diseases: it's all in the data
Genome-wide association analyses on large patient cohorts are generating large sets of candidate disease genes. This is coupled with the availability of ever-increasing genomic databases and a rapidly expanding repository of biomedical literature. Computational approaches to disease-gene association attempt to harness these data sources to identify the most likely disease gene candidates for further empirical analysis by translational researchers, resulting in efficient identification of genes of diagnostic, prognostic and therapeutic value. Existing computational methods analyze gene structure and sequence, functional annotation of candidate genes, characteristics of known disease genes, gene regulatory networks, protein-protein interactions, data from animal models and disease phenotype. To date, a few studies have successfully applied computational analysis of clinical phenotype data for specific diseases and shown genetic associations. In the near future, computational strategies will be facilitated by improved integration of clinical and computational research, and by increased availability of clinical phenotype data in a format accessible to computational approaches
A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a complex, multi-systemic, autoimmune disease for which the
underlying aetiological mechanisms are poorly understood. The genetic and molecular processes underlying lupus
have been extensively investigated using a variety of -omics approaches, including genome-wide association studies,
candidate gene studies and microarray experiments of differential gene expression in lupus samples compared to
controls.
METHODS: This study analyses a combination of existing microarray data sets to identify differentially regulated genetic
pathways that are dysregulated in human peripheral blood mononuclear cells from SLE patients compared to unaffected
controls. Two statistical approaches, quantile discretisation and scaling, are used to combine publicly available expression
microarray datasets and perform a meta-analysis of differentially expressed genes.
RESULTS: Differentially expressed genes implicated in interferon signaling were identified by the meta-analysis,
in agreement with the findings of the individual studies that generated the datasets used. In contrast to the
individual studies, however, the meta-analysis and subsequent pathway analysis additionally highlighted TLR
signaling, oxidative phosphorylation and diapedesis and adhesion regulatory networks as being differentially
regulated in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to controls.
CONCLUSION: Our analysis demonstrates that it is possible to derive additional information from publicly
available expression data using meta-analysis techniques, which is particularly relevant to research into rare
diseases where sample numbers can be limiting.Scopus & IS
Record linkage for routinely collected health data in an African health information exchange
The Patient Master Index (PMI) plays an important role in management of patient information and
epidemiological research, and the availability of unique patient identifiers improves the accuracy when
linking patient records across disparate datasets. In our environment, however, a unique identifier is
seldom present in all datasets containing patient information. Quasi identifiers are used to attempt to
link patient records but sometimes present higher risk of over-linking. Data quality and completeness
thus affect the ability to make correct linkages. This paper describes the record linkage system that is currently implemented at the Provincial Health
Data Centre (PHDC) in the Western Cape, South Africa, and assesses its output to date
An e-consent framework for tiered informed consent for human genomic research in the global south, implemented as a REDCap template
Research involving human participants requires their consent, and it is common practice to capture consent information
on paper and store those hard copies, presenting issues such as long-term storage requirements, inefficient
retrieval of consent forms for reference or future use, and the potential for transcription errors when transcribing
captured informed consent. There have been calls to move to electronic capture of the consent provided by research
participants (e-consent) as a way of addressing these issues. A tiered framework for e-consent was designed using
the freely available features in the inbuilt REDCap e-consent module. We implemented ‘branching logic’, ‘wet signature’
and ‘auto-archiver’ features to the main informed consent and withdrawal of consent documents. The branching
logic feature streamlines the consent process by making follow-up information available depending on participant
response, the ‘wet signature’ feature enables a timestamped electronic signature to be appended to the e-consent
documents and the ‘auto-archiver’ allows for PDF copies of the e-consent documents to be stored in the database.
When designing the content layout, we provided example participant information text which can be modified
as required. Emphasis was placed on the flow of information to optimise participant understanding and this was
achieved by merging the consent and participant information into one document where the consent questions were
asked immediately after the corresponding participant information. In addition, we have provided example text for a
generic human genomic research study, which can be easily edited and modified according to specific requirements.
Building informed consent protocols and forms without prior experience can be daunting, so we have provided
researchers with a REDCap template that can be directly incorporated into REDCap databases. It prompts researchers
about the types of consent they can request for genomics studies and assists them with suggestions for the language
they might use for participant information and consent questions. The use of this tiered e-consent module can ensure
the accurate and efficient electronic capture and storage of the consents given by participants in a format that can
be easily queried and can thus facilitate ethical and effective onward sharing of data and samples whilst upholding
individual participant preferences
Covid-19 among adults living with HIV: Correlates of mortality among public sector healthcare users in Western Cape, South Africa
Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty
about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the
association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.
Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection
(until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression
was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV
evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for
demographic characteristics, comorbidities, admission pressure, location and time period.
Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated
with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence,
differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more
recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality,
more strongly in younger adults
How to use relevant data for maximal benefit with minimal risk: Digital health data governance to protect vulnerable populations in low-income and middle- income countries
Globally, the volume of private and personal digital data has massively increased, accompanied by rapid expansion in the generation and use of digital health data. These technological advances promise increased opportunity
for data-driven and evidence-based health programme design, management and assessment; but also increased risk to individuals of data misuse or data breach of their sensitive personal data, especially given how easily
digital data can be accessed, copied and transferred on electronic platforms if the appropriate controls are not implemented. This is particularly pertinent in low-income and middle-income countries (LMICs), where vulnerable populations are more likely to be at a disadvantage in negotiating digital privacy and confidentiality given the intersectional nature of the digital divide. The potential benefits of strengthening health systems and improving health outcomes through the digital health environment thus come with a concomitant need to implement strong data governance structures and ensure the ethical use
and reuse of individuals’ data collected through digital health programmes. We present a framework for data governance to reduce the risks of health data breach or misuse in digital health programmes in LMICS. We define and describe four key domains for data governance and appropriate data stewardship, covering ethical oversight and informed consent processes, data protection through data access controls, sustainability of ethical data
use and application of relevant legislation. We discuss
key components of each domain with a focus on their relevance to vulnerable populations in LMICs and examples of data governance issues arising within the LMIC context
Computational Analysis of Candidate Disease Genes and Variants for Salt-Sensitive Hypertension in Indigenous Southern Africans
Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension
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