RESUMEN
PURPOSE: Biomedical databases combining electronic medical records and phenotypic and genomic data constitute a powerful resource for the personalization of treatment. To leverage the wealth of information provided, algorithms are required that systematically translate the contained information into treatment recommendations based on existing genotype-phenotype associations. METHODS: We developed and tested algorithms for translation of preexisting genotype data of over 44,000 participants of the Estonian biobank into pharmacogenetic recommendations. We compared the results obtained by genome sequencing, exome sequencing, and genotyping using microarrays, and evaluated the impact of pharmacogenetic reporting based on drug prescription statistics in the Nordic countries and Estonia. RESULTS: Our most striking result was that the performance of genotyping arrays is similar to that of genome sequencing, whereas exome sequencing is not suitable for pharmacogenetic predictions. Interestingly, 99.8% of all assessed individuals had a genotype associated with increased risks to at least one medication, and thereby the implementation of pharmacogenetic recommendations based on genotyping affects at least 50 daily drug doses per 1000 inhabitants. CONCLUSION: We find that microarrays are a cost-effective solution for creating preemptive pharmacogenetic reports, and with slight modifications, existing databases can be applied for automated pharmacogenetic decision support for clinicians.
Asunto(s)
Farmacogenética/métodos , Variantes Farmacogenómicas/genética , Análisis de Secuencia de ADN/métodos , Algoritmos , Bancos de Muestras Biológicas , Bases de Datos Factuales , Registros Electrónicos de Salud , Estonia , Pruebas Genéticas/normas , Genotipo , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Pruebas de Farmacogenómica/métodos , Fenotipo , Medicina de Precisión/métodosRESUMEN
The return of individual genomic results (ROR) to research participants is still in its early phase, and insight on how individuals respond to ROR is scarce. Studies contributing to the evidence base for best practices are crucial before these can be established. Here, we describe a ROR procedure conducted at a population-based biobank, followed by surveying the responses of almost 3000 participants to a range of results, and discuss lessons learned from the process, with the aim of facilitating large-scale expansion. Overall, participants perceived the information that they received with counseling as valuable, even when the reporting of high risks initially caused worry. The face-to-face delivery of results limited the number of participants who received results. Although the participants highly valued this type of communication, additional means of communication need to be considered to improve the feasibility of large-scale ROR. The feedback collected sheds light on the value judgements of the participants and on potential responses to the receipt of genetic risk information. Biobanks in other countries are planning or conducting similar projects, and the sharing of lessons learned may provide valuable insight and aid such endeavors.