ORCID Profile
0000-0002-1563-8168
Current Organisations
University of Tasmania
,
University of Melbourne
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Publisher: MDPI AG
Date: 19-02-2021
DOI: 10.3390/JPM11020144
Abstract: Neurological disorders pose a substantial health and economic burden to the in idual and society, necessitating strategies for effective prevention and disease management. Lifestyle behaviours play a role in risk and management of some neurological disorders however, overlap between lifestyle behaviours across disorders has not been well explored. We used log-binomial regression to assess associations of selected lifestyle behaviours in community-dwelling Australians (n = 192,091), some of whom self-reported Alzheimer’s disease (AD), motor neurone disease (MND), multiple sclerosis (MS), Parkinson’s disease (PD) or stroke. Of six lifestyle behaviours, undertaking physical activity was inversely associated with the presence of all neurological disorders except PD. Smoking was positively associated with MND and stroke, and inversely associated with PD. Participants with AD and stroke shared inverse associations with cognitive engagement, face-to-face social interaction and stress-reducing activities, and MS was positively associated with online social interaction and stress-reduction activities. Of eleven food and beverage consumption categories, no associations were seen in MND, ten categories were inversely associated with people with AD or stroke, and six of these with PD. Vegetable and soft drink consumption were associated with MS. Further detailed assessment of commonalities in lifestyle behaviours across neurological disorders may inform potential strategies for risk reduction across disorders.
Publisher: Oxford University Press (OUP)
Date: 08-11-2022
Abstract: Understanding how variations in the plasma and brain proteome contribute to multiple sclerosis susceptibility can provide important insights to guide drug repurposing and therapeutic development for multiple sclerosis. However, the role of genetically predicted protein abundance in multiple sclerosis remains largely unknown. Integrating plasma proteomics (n = 3,301) and brain proteomics (n = 376 discovery n = 152 replication) into multiple sclerosis genome-wide association studies (n = 14,802 cases and 26,703 controls), we employed summary-based methods to identify candidate proteins involved in multiple sclerosis susceptibility. Next, we evaluated associations of the corresponding genes with multiple sclerosis at tissue-level using large gene expression quantitative trait data from whole-blood (n = 31,684) and brain (n = 1,194) tissue. Further, to assess transcriptional profiles for candidate proteins at cell-level, we examined gene expression patterns in immune cell types (dataset 1: n = 73 cases and 97 controls dataset 2: n = 31 cases and 31 controls) for identified plasma proteins, and in brain cell types (dataset 1: n = 4 cases and 5 controls dataset 2: n = 5 cases and 3 controls) for identified brain proteins. In a longitudinal multiple sclerosis cohort (n = 203 cases followed up to 15 years), we also assessed the corresponding gene-level associations with the outcome of disability worsening. We identified 39 novel proteins associated with multiple sclerosis risk. Based on five identified plasma proteins, four available corresponding gene candidates showed consistent associations with multiple sclerosis risk in whole-blood, and we found TAPBPL upregulation in multiple sclerosis B cells, CD8+ T cells and natural killer cells compared to controls. Among the 34 candidate brain proteins, 18 were replicated in a smaller cohort and 14 of 21 available corresponding gene candidates also showed consistent associations with multiple sclerosis risk in brain tissue. In cell-specific analysis, six identified brain candidates showed consistent differential gene expression in neuron and oligodendrocyte cell clusters. Based on the 39 protein-coding genes, we found 23 genes that were associated with disability worsening in multiple sclerosis cases. The findings present a set of candidate protein biomarkers for multiple sclerosis, reinforced by high concordance in downstream transcriptomics findings at tissue-level. This study also highlights the heterogeneity of cell-specific transcriptional profiles for the identified proteins, and that numerous candidates were also implicated in disease progression. Together, these findings can serve as an important anchor for future studies of disease mechanisms and therapeutic development.
Publisher: BMJ
Date: 02-02-2023
Abstract: There are currently no specific biomarkers for multiple sclerosis (MS). Identifying robust biomarkers for MS is crucial to improve disease diagnosis and management. This study first used six Mendelian randomisation methods to assess causal relationship of 174 metabolites with MS, incorporating data from European-ancestry metabolomics (n=8569–86 507) and MS (n=14 802 MS cases, 26 703 controls) genomewide association studies. Genetic scores for identified causal metabolite(s) were then computed to predict MS disability progression in an independent longitudinal cohort (AusLong study) of 203 MS cases with up to 15-year follow-up. We found a novel genetic causal effect of serine on MS onset (OR=1.67, 95% CI 1.51 to 1.84, p=1.73×10 −20 ), such that in iduals whose serine level is 1 SD above the population mean will have 1.67 times the risk of developing MS. This is robust across all sensitivity methods (OR ranges from 1.49 to 1.67). In an independent longitudinal MS cohort, we then constructed time-dynamic and time-fixed genetic scores based on serine genetic instrument single-nucleotide polymorphisms, where higher scores for raised serum serine level were associated with increased risk of disability worsening, especially in the time-dynamic model (RR=1.25, 95% CI 1.10 to 1.42, p=7.52×10 −4 ). These findings support investigating serine as an important candidate biomarker for MS onset and disability progression.
Publisher: MDPI AG
Date: 15-08-2020
Abstract: Health communication offers an important means for patients to make informed decisions for illness self-management. We assessed how the level of engagement with selected health information at baseline is associated with the adoption and maintenance of lifestyle behaviours at a 5-year follow-up in people with multiple sclerosis (MS). Non-engagers were compared to engagers of information delivered online and print (medium), and with engagers who additionally attended a live-in workshop (high). Engagement was assessed against lifestyle behaviours by log-binomial regression. Information engagers had higher education, and were less likely to have severe disability, clinically significant fatigue, or obesity. Medium and high baseline engagement was associated with adopting healthy behaviours for omega 3 supplementation (RR = 1.70 95%CI: 1.02–2.84), physical activity (RR = 2.16 95%CI: 1.03–4.55), and dairy non-consumption (RR = 3.98 95%CI: 1.85–8.56) at 5 years associations were stronger among high engagers. Only high baseline engagement was associated with maintaining behaviours from baseline to 5 years, specifically for omega-3 (RR = 1.26 95%CI: 1.06–1.49) and vitamin D supplementation (RR = 1.26 95%CI: 1.04–1.54) and dairy non-consumption (RR = 1.47 95%CI: 1.03–2.10). Health communication that includes face-to-face information delivery and practical tools for implementation in daily living may be optimal for adopting and maintaining lifestyle behaviours in people with MS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-05-2022
DOI: 10.1212/NXG.0000000000200005
Abstract: Advances in genome sequencing technologies have unlocked new possibilities in identifying disease-associated and causative genetic markers, which may in turn enhance disease diagnosis and improve prognostication and management strategies. With the capability of examining genetic variations ranging from single-nucleotide mutations to large structural variants, whole-genome sequencing (WGS) is an increasingly adopted approach to dissect the complex genetic architecture of neurologic diseases. There is emerging evidence for different structural variants and their roles in major neurologic and neurodevelopmental diseases. This review first describes different structural variants and their implicated roles in major neurologic and neurodevelopmental diseases, and then discusses the clinical relevance of WGS applications in neurology. Notably, WGS-based detection of structural variants has shown promising potential in enhancing diagnostic power of genetic tests in clinical settings. Ongoing WGS-based research in structural variations and quantifying mutational constraints can also yield clinical benefits by improving variant interpretation and disease diagnosis, while supporting biomarker discovery and therapeutic development. As a result, wider integration of WGS technologies into health care will likely increase diagnostic yields in difficult-to-diagnose conditions and define potential therapeutic targets or intervention points for genome-editing strategies.
No related grants have been discovered for Xin Lin.