Principal Investigator: Dr Françoise Fougerousse
Department: Institut de Recherches Internationales Servier, Suresnes, France
Dr Celine Lefebvre, Institut de Recherches Servier (IDRS), Croissy sur Seine, France
Tags: 53401, Association, featured, genetics/genotyping, GWAS, Heart failure, Mendelian randomisation, variant
Heart failure with preserved ejection fraction (HFpEF) represents around half of all heart failure patients. The prevalence of this disease is rising at a rate of around 1% by year. The pharmacotherapy did not improve the prognostic in HFpEF as all large randomised trials have yielded neutral results. High cost of randomised controlled trials and feasibility problems may pose further challenges in their implementation. Therefore, we need alternative approaches for testing causal relationships in research that can provide reliable evidence for causal associations.
Genetics can be a very useful tool in the discovery and validation of therapeutic targets. Genome-wide association studies (GWAS) identify loci associated to a phenotype or trait under study. The major limitations of GWAS are that the identified sequence variants do not need to be causally related to the phenotype in question and provide no information about the associated pathophysiological mechanism, which therefore has to be identified through specific functional studies. With Mendelian randomisation (MR), genetic variants can be used as tools to determine whether the association between a biomarker and a disease is causal, which is a prerequisite for the biomarker’s candidacy as a therapeutic target. MR can be used to predict the results of planned clinical trials before they are complete, and so de-risk the exorbitantly expensive drug development process. The methodology for MR approach is well established and is currently implemented in the development of heart failure drugs. This innovative tool will be used to identify factors influencing disease progression and represent a huge opportunity to develop new treatments.
Last updated Nov 11, 2019