Ozvan Bocher
A5032934721- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetic and phenotypic traits in livestock
- Liver Disease Diagnosis and Treatment
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Diet and metabolism studies
- Forensic and Genetic Research
- Molecular Biology Techniques and Applications
- Cystic Fibrosis Research Advances
- Birth, Development, and Health
- Dietary Effects on Health
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Folate and B Vitamins Research
- Forensic Anthropology and Bioarchaeology Studies
- Metabolomics and Mass Spectrometry Studies
- Genetic Syndromes and Imprinting
- Neurological Disease Mechanisms and Treatments
- Neonatal Respiratory Health Research
- Race, Genetics, and Society
- Prenatal Screening and Diagnostics
- Reproductive System and Pregnancy
Helmholtz Zentrum München
2022-2025
École nationale d'ingénieurs de Brest
2019-2024
Inserm
2019-2024
Université de Bretagne Occidentale
2019-2024
Génétique, Génomique Fonctionnelle et Biotechnologies
2020-2024
Genomics (United Kingdom)
2024
Center for Environmental Health
2022-2024
Centre Hospitalier Régional Universitaire de Brest
2021
University Hospital of Wales
2021
Abstract Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes 1,2 and molecular mechanisms are often specific to cell type 3,4 . Here, characterize the genetic contribution these across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases T2D. We identify 1,289 independent signals at significance ( P < 5 × 10 −8 ) map 611 loci, which 145...
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent signals at significance (P<5×10 − 8 ) map 611 loci, of which 145 loci are previously unreported. define eight non-overlapping...
Whole genome sequencing has enabled new insights into the genetic architecture of complex traits, especially through access to low-frequency and rare variation. This Comment highlights key contributions from this technology discusses considerations for its use future perspectives.
Abstract Imputation servers offer the exclusive possibility to harness largest public reference panels which have been shown deliver very high precision in imputation of European genomes. Many studies nonetheless stressed importance ‘study specific panels’ (SSPs) as an alternative and benefits combining with SSPs. But such combined approaches are not attainable when using external servers. To investigate how confront this challenge, we imputed 550 French individuals either University...
Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic proteomic profiles between dietary states a unique group of individuals who alternate omnivory restriction animal products religious reasons. We find that short-term drives reductions levels lipid classes branched-chain amino acids, not detected control individuals,...
Abstract Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information 16 multi-tissue and multi-ancestry expression, protein, metabolite quantitative trait loci (QTL) 46 GWAS for T2D-related traits with largest, most ancestrally diverse T2D to date. Of 1,289 index variants, 716 (56%) demonstrated strong evidence of colocalization molecular or trait, implicating 657 cis...
The demographical history of France remains largely understudied despite its central role toward understanding modern population structure across Western Europe. Here, by exploring publicly available Europe-wide genotype datasets together with the genomes 3234 present-day and six newly sequenced medieval individuals from Northern France, we found extensive fine-scale Brittany downstream Loire basin increased differentiation between northern southern sides river Loire, associated higher...
Genotype-phenotype association tests are typically adjusted for population stratification using principal components that estimated genome-wide. This lacks resolution when analysing populations with fine structure and/or individuals levels of admixture. can affect power and precision, is a particularly relevant consideration control recruited geographic selection criteria. Such the case in France where we have recently created reference panels anchored to different regions. To make correct...
Rare variant association tests (RVAT) have been developed to study the contribution of rare variants widely accessible through high-throughput sequencing technologies. RVAT require aggregate in testing units and filter retain only most likely causal ones. In exome, genes are natural usually filtered based on their functional consequences. However, when dealing with whole-genome sequence (WGS) data, both steps challenging. No biological unit is available for aggregating variants. Sliding...
Genetic association studies have provided new insights into the genetic variability of human complex traits with a focus mainly on continuous or binary traits. Methods been proposed to take account disease heterogeneity between subgroups patients when studying common variants but none was specifically designed for rare variants. Because are expected stronger effects and be more heterogeneously distributed among cases than ones, subgroup analyses might particularly attractive in this context....
Genetic prediction of common complex disease risk is an essential component precision medicine. Currently, genome-wide association studies (GWASs) are mostly composed European-ancestry samples and resulting polygenic scores (PGSs) have been shown to poorly transfer other ancestries partly due heterogeneity allelic effects between populations. Fixed-effects (FETA) random-effects (RETA) trans-ancestry meta-analyses do not model such ancestry-related heterogeneity, while ancestry-specific (AS)...
ABSTRACT The introduction of Next‐Generation Sequencing technologies in the clinics has improved rare disease diagnosis. Nonetheless, for very heterogeneous or diseases, more than half cases still lack molecular Novel strategies are needed to prioritize variants within a single individual. Population Sampling Probability (PSAP) method was developed meet this aim but only coding exome data. Here, we propose an extension PSAP non‐coding genome called PSAP‐genomic‐regions. In extension, instead...
Abstract European genetic ancestry originates from three main ancestral populations - Western hunter-gatherers, early farmers and Yamnaya Eurasian herders whose edges geographically met in present-day France. Despite its central role to our understanding of how the interacted gave rise modern population structure, history France has remained largely understudied. Here, we analysed high-coverage whole-genome sequences genome-wide genotype profiles respectively 856 3,234 individuals northern...
Abstract Next‐generation sequencing technologies have opened up the possibility to sequence large samples of cases and controls test for association with rare variants. To limit cost increase sample sizes, data from could be used in multiple studies might thus generated on different platforms. This pose some problems comparability between due batch effects that confounding factors, leading false‐positive signals. ensure datasets, stringent quality are required. We propose an integrative...
About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions CREs, described as “cis-ruptions” have been identified being involved in various genetic diseases. Thanks to development chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory were identified, but mechanisms CFTR gene yet be fully elucidated. The aim this work improve our knowledge regulation, and identity factors that...
Abstract The introduction of next generation sequencing technologies in the clinics has improved rare disease diagnosis. Nonetheless, for very heterogeneous or diseases, more than half cases still lack molecular Novel strategies are needed to prioritize variants within a single individual. PSAP (Population Sampling Probability) method was developed meet this aim but only coding exome data. To address challenge analysis non-coding whole genome data, we propose an extension called...
Abstract Objectives Dietary interventions can be a powerful tool for the prevention and treatment of diseases, but molecular mechanisms through which diet affects health remain underexplored in humans. Generating robust evidence on impact specific dietary patterns humans will help us harness power to improve health. Methods Here, we compare plasma metabolomic proteomic profiles between states unique group individuals (N=200) who alternate omnivory restriction animal products religious...
Multiple molecular mechanisms are involved in the pathogenesis of type 2 diabetes (T2D), with potentially different effects across ancestries. Recent large-scale efforts by Type Diabetes Global Genomics Initiative (T2DGGI) have broadly described genetic architecture T2D, data that can be subsequently used to pinpoint causal leading T2D an ancestry-aware manner. In this work, we sought explore gene expression and proteins on ancestries leveraging from latest T2DGGI multi-ancestry genome-wide...
Abstract Circulating metabolite levels have been associated with type 2 diabetes (T2D), but the extent to which these are affected by T2D and involvement of genetics in mediating relationships remain be elucidated. In this study, we investigate interplay between genetics, metabolomics risk UK Biobank dataset. We find 79 metabolites a causal association T2D, mostly spanning lipid-related classes, while twice as many causally liability, including branched-chain amino acids. Secondly, using an...
Circulating metabolite levels have been associated with type 2 diabetes (T2D), but the extent to which T2D affects and their genetic regulation remains be elucidated. In this study, we investigate interplay between genetics, metabolomics, risk in UK Biobank dataset using Nightingale panel composed of 249 metabolites, 92% correspond lipids (HDL, IDL, LDL, VLDL) lipoproteins. By integrating these data large-scale GWAS from DIAMANTE meta-analysis through Mendelian randomization analyses, find...
Abstract Stroke is a leading cause of acute death related in part to brain oedema, blood–brain barrier disruption and glial inflammation. A cyclin-dependant kinase inhibitor, (S)-roscovitine, was administered 90 min after onset on model rat focal cerebral ischaemia. Brain swelling Evans Blue tissue extravasation were quantified injection. Combined fluorescence immunofluorescence endothelial cells (RECA1), microglia (isolectin-IB4) astrocytes (glial fibrillary acidic protein) analysed. Using...