Pharmacogenomics of antithrombotic drugs –a novel study design and data collection approach using Finnish biobanks and national registries

Aim: With aging population, the need for individualised antithrombotic treatments will expand. Pharmacogenetic studies have established associations between a number of genetic variants and adverse drug responses with antithrombotic drugs. This abstract presents the design of a register linkage study, which aims to investigate the clinical and economic feasibility of using genomic data in the context of antithrombotic drug therapy.
Methods: This is a retrospective cohort study linking data from three Finnish biobanks (Helsinki Biobank, Auria Biobank and THL Biobank), national registries of National Institute of Health and Welfare (THL) and the Social Insurance Institution (Kela) and laboratory databases to investigate the feasibility of using genotype data in antithrombotic therapy. Based on earlier research, data regarding 23 genetic variants will be used for the analyses. Genotype data generated within the FinnGen project and scheduled to be available for biobank research during 2019 will be used. Individuals with and without specific variant alleles are compared in respect to their response to warfarin therapy measured by the incidence of bleeding complications and the time in therapeutic range (TTR) parameter. Individuals are also analysed in relation to other clinical outcomes and healthcare encounters, and possible interactions with other drugs. Furthermore, the explorative part of the study will employ data-driven classification methods to investigate genotype-phenotype associations for a larger group of antithrombotic drugs, including direct oral anticoagulants, clopidogrel and heparins.
Results: Data permit applications to the registry holders have been submitted during the first quarter of 2019. The first results are expected to be available during 2019. The early estimate on sample size indicates that by combining data from three biobanks approximately 2600 adults with genotype data will be available which suffices the predefined power for the study. Beyond the clinical results, the study sheds light on the process of combining data from several biobanks. Such information is expected to be valuable for the on-going development of centralized register data and biobank services in Finland.
Conclusions: The study increases the understanding of pharmacogenomics of antithrombotic drugs in the Finnish population and assesses the need for genotype-guided therapy to improve the outcomes of antithrombotic therapies.