ORCID Profile
0000-0001-8880-9311
Current Organisations
KU Leuven
,
Monash Health
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Publisher: Elsevier BV
Date: 2021
Publisher: Cold Spring Harbor Laboratory
Date: 15-03-2021
DOI: 10.1101/2021.03.12.21253159
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced in iduals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Across environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.
Publisher: Cold Spring Harbor Laboratory
Date: 24-03-2021
DOI: 10.1101/2021.03.12.21253115
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 s les (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.
Publisher: Springer Science and Business Media LLC
Date: 05-06-2021
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-02-2022
DOI: 10.1126/SCITRANSLMED.ABJ0264
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 s les passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Oxford University Press (OUP)
Date: 13-06-2014
DOI: 10.1093/HMG/DDU300
Publisher: Springer Science and Business Media LLC
Date: 31-03-2022
DOI: 10.1038/S41593-022-01040-6
Abstract: The noncoding genome is substantially larger than the protein-coding genome but has been largely unexplored by genetic association studies. Here, we performed region-based rare variant association analysis of >25,000 variants in untranslated regions of 6,139 amyotrophic lateral sclerosis (ALS) whole genomes and the whole genomes of 70,403 non-ALS controls. We identified interleukin-18 receptor accessory protein (IL18RAP) 3' untranslated region (3'UTR) variants as significantly enriched in non-ALS genomes and associated with a fivefold reduced risk of developing ALS, and this was replicated in an independent cohort. These variants in the IL18RAP 3'UTR reduce mRNA stability and the binding of double-stranded RNA (dsRNA)-binding proteins. Finally, the variants of the IL18RAP 3'UTR confer a survival advantage for motor neurons because they d en neurotoxicity of human induced pluripotent stem cell (iPSC)-derived microglia bearing an ALS-associated expansion in C9orf72, and this depends on NF-κB signaling. This study reveals genetic variants that protect against ALS by reducing neuroinflammation and emphasizes the importance of noncoding genetic association studies.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1038/GIM.2016.147
Publisher: Springer Science and Business Media LLC
Date: 23-04-2019
DOI: 10.1038/S41467-019-09671-3
Abstract: Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni 1.06 x 10 −7 ). In additional analyses in 7,278 participants, .3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.51893/2021.1.OA10
Abstract: Objectives: The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) provides a standardised method for measuring health and disability. This study aimed to determine its reliability, validity and responsiveness and to establish the minimum clinically important difference (MCID) in critically ill patients. Design: Prospective, multicentre cohort study. Setting: Intensive care units of six metropolitan hospitals. Participants: Adults mechanically ventilated for 24 hours. Main outcome measures: Reliability was assessed by measuring internal consistency. Construct validity was assessed by comparing WHODAS 2.0 scores at 6 months with the EuroQoL visual analogue scale (EQ VAS) and Lawton Instrumental Activities of Daily Living (IADL) scale scores. Responsiveness was evaluated by assessing change over time, effect sizes, and percentage of patients showing no change. The MCID was calculated using both anchor and distribution-based methods with triangulation of results. Main results: A baseline and 6-month WHODAS 2.0 score were available for 448 patients. The WHODAS 2.0 demonstrated good correlation between items with no evidence of item redundancy. Cronbach α coefficient was 0.91 and average split-half coefficient was 0.91. There was a moderate correlation between the WHODAS 2.0 and the EQ VAS scores (r = 0.72 P 0.001) and between the WHODAS 2.0 and the Lawton IADL scores (r = 0.66 P 0.001) at 6 months. The effect sizes for change in the WHODAS 2.0 score from baseline to 3 months and from 3 to 6 months were low. Ceiling effects were not present and floor effects were present at baseline only. The final MCID estimate was 10%. Conclusion: The 12-item WHODAS 2.0 is a reliable, valid and responsive measure of disability in critically ill patients. A change in the total WHODAS 2.0 score of 10% represents the MCID.
Publisher: Frontiers Media SA
Date: 09-11-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-05-2021
DOI: 10.1097/CCM.0000000000005058
Abstract: To determine the influence of active mobilization during critical illness on health status in survivors 6 months post ICU admission. Post hoc secondary analysis of a prospective cohort study conducted between November 2013 and March 2015. Two tertiary hospital ICU’s in Victoria, Australia. Of 194 eligible patients admitted, mobility data for 186 patients were obtained. Inclusion and exclusion criteria were as per the original trial. The dosage of mobilization in ICU was measured by: 1) the Intensive Care Mobility Scale where a higher Intensive Care Mobility Scale level was considered a higher intensity of mobilization or 2) the number of active mobilization sessions performed during the ICU stay. The data were extracted from medical records and analyzed against Euro-quality of life-5D-5 Level version answers obtained from phone interviews with survivors 6 months following ICU admission. The primary outcome was change in health status measured by the Euro-quality of life-5D-5 Level utility score, with change in Euro-quality of life-5D-5 Level mobility domain a secondary outcome. Achieving higher levels of mobilization (as per the Intensive Care Mobility Scale) was independently associated with improved outcomes at 6 months (Euro-quality of life-5D-5 Level utility score unstandardized regression coefficient [ β ] 0.022 [95% CI, 0.002–0.042] p = 0.033 Euro-quality of life-5D-5 Level mobility domain β = 0.127 [CI, 0.049–0.205] p = 0.001). Increasing the number of active mobilization sessions was not found to independently influence health status. Illness severity, total comorbidities, and admission diagnosis also independently influenced health status. In critically ill survivors, achieving higher levels of mobilization, but not increasing the number of active mobilization sessions, improved health status 6 months after ICU admission.
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2018
DOI: 10.1101/377911
Abstract: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease affecting 1 in 350 people. The aim of Project MinE is to elucidate the pathophysiology of ALS through whole-genome sequencing at least 15,000 ALS patients and 7,500 controls at 30X coverage. Here, we present the Project MinE data browser ( databrowser.projectmine.com ). a unique and intuitive one-stop, open-access server that provides detailed information on genetic variation analyzed in a new and still growing set of 4,366 ALS cases and 1,832 matched controls. Through its visual components and interactive design, the browser specifically aims to be a resource to those without a biostatistics background and allow clinicians and preclinical researchers to integrate Project MinE data into their own research. The browser allows users to query a transcript and immediately access a unique combination of detailed (meta)data, annotations and association statistics that would otherwise require analytic expertise and visits to scattered resources.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.CCC.2018.06.005
Abstract: This article outlines the effect of early mobilization on the long-term recovery of patients following critical illness. It investigates the safety of performing exercise in this environment, the differing types of rehabilitation that can be provided, and the gaps remaining in evidence around this area. It also attempts to assist clinicians in prescription of exercise in this cohort while informing all readers about the impact that mobilization can have for the outcomes of intensive care patients.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 28-06-2018
Publisher: Wiley
Date: 15-01-2021
DOI: 10.1002/ANA.26009
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.APMR.2018.03.015
Abstract: The aim of this systematic review was to identify the effect of specific exercise parameters on physical function and quality of life (QOL) in people with chronic heart failure living in the community. A total of 5 electronic databases were searched for relevant studies published after 1994. The screening process was completed by 2 independent researchers, with a third independent reviewer for conflict resolution. Studies were selected if they included only chronic hHart failure participants, and the sole intervention was a structured exercise training program in an outpatient or community setting. Two independent researchers completed the data extraction and qualiy assessment. Quality was assessed using the Physiotherapy Evidence Database and Grading of Recommendations Assessment, Development and Evaluation scales. In total, 40 articles (n=5411) were included in the review for meta-analysis and meta-regression, including 27 randomized control trials and 13 cohort studies. Exercise was shown to have a positive effect on QOL outcomes (standardized mean difference 1.16 95% confidence interval [CI], 0.76-1.56) with the most commonly used measure, the Minnesota Living with Heart Failure Questionnaire, showing a clinically significant change of 8.5 points. Physical function was improved postexercise intervention in the 23 included studies (standardized mean difference 0.89 95% CI, 0.40-1.38), with a clinically significant change of 49.8 m seen in studies using the 6-minute walk test (95% CI, 26.52-73.13). These improvements were independent of study design, study quality, participant demographics, disease severity, and exercise prescription variables. Exercise significantly improves QOL and physical function. Current evidence suggests that engagement with exercise is a more important factor in achieving improvement than how the exercise is performed. Future research should aim to identify and address barriers to engagement in exercise rehabilitation in this population.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2022
DOI: 10.1038/S41525-021-00267-9
Abstract: There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Informa UK Limited
Date: 13-12-2017
Publisher: Wiley
Date: 07-2018
DOI: 10.1002/ANA.25273
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Matthieu Moisse.