A5013720328- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Gestational Diabetes Research and Management
- Genetic Associations and Epidemiology
- Birth, Development, and Health
- Genetics and Neurodevelopmental Disorders
- Prenatal Substance Exposure Effects
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Liver Disease Diagnosis and Treatment
- Genetic Mapping and Diversity in Plants and Animals
- Pancreatic and Hepatic Oncology Research
- Genomics and Chromatin Dynamics
- Pancreatitis Pathology and Treatment
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- FOXO transcription factor regulation
- Genetic Syndromes and Imprinting
- Diabetes Treatment and Management
- Soft tissue tumor case studies
- Machine Learning in Bioinformatics
- Lipoproteins and Cardiovascular Health
- Endoplasmic Reticulum Stress and Disease
European Genomic Institute for Diabetes
2019-2024
Institut Pasteur de Lille
2019-2024
Inserm
2020-2024
Centre National de la Recherche Scientifique
2019-2024
Université de Lille
2019-2024
Imperial College London
2019-2024
Hammersmith Hospital
2023-2024
Genomics England
2019-2022
Centre Hospitalier Universitaire de Lille
2020-2021
(Epi)génomique fonctionnelle métabolique et des dysfonctions dans le diabète de type 2 et des maladies associées
2020-2021
Depression is a common comorbidity of type 2 diabetes. We assessed the causal relationships and shared genetics between them.We applied two-sample, bidirectional Mendelian randomization (MR) to assess causality diabetes depression. investigated potential mediation using two-step MR. To identify genetics, we performed 1) genome-wide association studies (GWAS) separately 2) multiphenotype GWAS (MP-GWAS) (19,344 case subjects, 463,641 control subjects) depression major depressive disorder (MDD)...
Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human dysfunction induced by metabolic stress reversible, evaluate the molecular pathways underlying persistent or transient damage, explore relationships with T2D islet traits. Twenty-six preparations are exposed several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, combination. The reversal occurs after washout for...
Type 2 diabetes (T2D) and hypertension are common health conditions that often occur together, suggesting shared biological mechanisms. To explore this relationship, we analysed large-scale multiomic data to uncover genetic factors underlying T2D blood pressure (BP) comorbidity. We curated 1,304 independent single-nucleotide variants (SNVs) associated with T2D/BP, grouping them into five clusters related metabolic syndrome, inverse T2D-BP risk, impaired pancreatic beta-cell function, higher...
Genome wide association studies (GWAS) for type 2 diabetes (T2D) have identified genetic loci that often localise in non-coding regions of the genome, suggesting gene regulation effects. We combined and transcriptomic analysis from human islets obtained brain-dead organ donors or surgical patients to detect expression quantitative trait (eQTLs) shed light into regulatory mechanisms these genes.Pancreatic were isolated either by laser capture microdissection (LCM) specimens 103 metabolically...
OBJECTIVE Gestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later life, which might be explained by epigenetic changes response to maternal hyperglycemic exposure. RESEARCH DESIGN AND METHODS We explored the association between GDM exposure blood newborn cord methylation 536 mother-offspring pairs from prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. assessed two hypotheses. First, we tested...
Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), C-terminus of secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be sole driver T2D risk locus, recent studies have provided evidence for lowered expression mRNA in protective allele carriers. In present study, we examined multiple variants that influence allele-specific...
Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disease characterised by increased low-density lipoprotein cholesterol (LDL-C) levels. The functionality of four novel variants within the LDLR 5′UTR and promoter located at c.-13A>G, c.-101T>C, c.-121T>C c.-215A>G was investigated using in silico vitro assays, a systemic bioinformatics analysis all 36 reported are presented. Bioinformatic tools predicted that occurred sites likely to bind transcription factors binding...
Human functional genomics has proven powerful in discovering drug targets for common metabolic disorders. Through this approach, we investigated the involvement of purinergic receptor P2RY1 type 2 diabetes (T2D). was sequenced 9,266 participants including 4,177 patients with T2D. In vitro analyses were then performed to assess effect each variant. Expression quantitative trait loci (eQTL) analysis pancreatic islets from 103 pancreatectomized individuals. The on glucose-stimulated insulin...
We postulated that type 2 diabetes (T2D) predisposes patients to exocrine pancreatic diseases through (epi)genetic mechanisms. explored the methylome (using MethylationEPIC arrays) of pancreas in 141 donors, assessing impact T2D. An epigenome-wide association study T2D identified hypermethylation an enhancer lipase–related protein 1 (PNLIPRP1) gene, associated with decreased PNLIPRP1 expression. null variants (found 191,000 participants UK Biobank) were elevated glycemia and LDL cholesterol....
Abstract Background Adipogenesis, the process whereby preadipocytes differentiate into mature adipocytes, is crucial for maintaining metabolic homeostasis. Cholesterol-lowering statins increase type 2 diabetes (T2D) risk possibly by affecting adipogenesis and insulin resistance but (epi)genetic mechanisms involved are unknown. Here, we characterised effects of statin treatment on adipocyte differentiation using in vitro human preadipocyte cell model to identify putative effective genes....
Diabet. Med. 28, 681–684 (2011) Abstract Aim Genome‐wide association studies have identified > 30 common variants associated with Type 2 diabetes (> 5% minor allele frequency). These small effects on individual risk and do not account for a large proportion of the heritable component disease. Monogenic forms are caused by mutations that occur in < 1:2000 individuals follow strict patterns inheritance. In contrast, role low frequency genetic (minor 0.1–5%) is known. The aim this...
Using chromatin conformation capture, we show that an enhancer cluster in the STARD10 type 2 diabetes (T2D) locus forms a defined 3-dimensional (3D) domain. A 4.1-kb region within this locus, carrying 5 T2D-associated variants, physically interacts with CTCF-binding regions and possessing strong transcriptional activity. Analysis of human islet 3D interaction maps identifies FCHSD2 gene as additional target cluster. CRISPR-Cas9-mediated deletion variant region, or associated enhancer, from...
<p dir="ltr"><b>Abstract:</b></p><p dir="ltr">We postulated that T2D predisposes to exocrine pancreatic diseases through (epi)genetic mechanisms. We explored the methylome (methylationEPIC arrays) of pancreas 141 donors, assessing impact T2D. Epigenome-wide association study (EWAS) for identified a hypermethylation in an enhancer Pancreatic-Lipase-Related-Protein 1 (<i>PNLIPRP1</i>) gene, associated with decreased <i>PNLIPRP1</i>...
<p dir="ltr"><b>Abstract:</b></p><p dir="ltr">We postulated that T2D predisposes to exocrine pancreatic diseases through (epi)genetic mechanisms. We explored the methylome (methylationEPIC arrays) of pancreas 141 donors, assessing impact T2D. Epigenome-wide association study (EWAS) for identified a hypermethylation in an enhancer Pancreatic-Lipase-Related-Protein 1 (<i>PNLIPRP1</i>) gene, associated with decreased <i>PNLIPRP1</i>...
ABSTRACT Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs subsequent diagnosis type 2 (T2D). To improve our understanding the aetiological factors molecular processes driving occurrence GDM, including extent to which these overlap T2D pathophysiology, GENetics Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) diverse ancestry in a total 5,485 women...
<i>Objective: </i>Gestational diabetes mellitus (GDM) is associated with a future offspring risk for the development of obesity and insulin resistance in Gestational an increased later life, which might be explained by epigenetic changes response to maternal hyperglycaemic exposure. <p><i>Research Design Methods: </i>We explored association GDM exposure on blood newborn cord-blood methylation 536 mother-offspring pairs from prospective FinnGeDi cohort, using...
SUMMARY Genome-wide association studies have identified thousands of genetic variants associated with type 2 diabetes (T2D) risk. Using chromatin conformation capture we show that an enhancer cluster in the STARD10 T2D locus forms a defined 3D domain. A 4.1 Kb region within this region, carrying five disease-associated variants, physically interacts CTCF-binding regions and possessing strong transcriptional activity. Analysis human islet interaction maps identifies FCHSD2 gene as additional...
Abstract Background Type 2 diabetes (T2D) increases the risk of pancreatic ductal adenocarcinoma (PDAC), which could be due to an epigenetic mechanism. Methods We explored association between T2D and whole pancreas methylation in 141 individuals, 28 had T2D, using Illumina MethylationEPIC 850K BeadChip arrays. performed downstream functional assessment rat acinar cell line AR42J. To further understand role our candidate gene humans, we tested whether null variants were associated with...
Abstract Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), C-terminus of secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be sole driver T2D risk locus, recent studies have provided evidence for lowered expression mRNA in protective allele carriers. In present study, combined allele-specific (cASE) analysis human islets...