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Adrien Georges, Thomas Cloatre, Lu Liu, Délia Dupré, Siying Huang, Romain Glandier, Takiy Berrandou, ARCADIA study, Nabila Bouatia-Naji (PARCC/HEGP, Paris, France)
Genome-wide association studies (GWAS) analyse the role of common genetic variants in the susceptibility to complex genetic diseases, such as cardiovascular diseases (CVD). Fibromuscular Dysplasia (FMD) is an arterial disease and a cause of hypertension, stroke and myocardial infarction affecting mostly early middle-aged women with few cardiovascular risk factors, (e.g age, dyslipidaemia). To elucidate the biological mechanism behind arterial loss of integrity in FMD (mainly through stenosis, aneurysm and dissection), we realized the first case control GWAS for FMD. We identified several associated loci involving non-coding variants in genomic regions with potential arterial cell-specific regulatory properties. We use multiple high-throughput genomic techniques (ATAC-Seq, ChIP-Seq and 4C-Seq) to generate extensive and comprehensive annotations, aiming to identify the causal variants and targeted genes at GWAS loci. Biology experiments on arterial cell models will inform the regulation and mechanism of action of FMD genes, which is a mandatory step prior to improve our understanding of FMD and ultimately contribute to its specific management as a CVD predominantly affecting women.http://parcc.inserm.fr/research-teams/team/bouatia-naji-jeunemaitre/