Principal Investigator: Dr Marieke Coenen
Radboud University Medical Centre, NetherlandsTags: 52524, adverse drug reaction, genome-wide association analysis, medicines, Pharmacogenomics, side-effects, treatment outcome
Many patients experience health care related adverse drug events, part of these even lead to hospital admission and mortality, indicating that there is not only considerable harm but also a large economic burden. Indeed, several studies have shown that costs associated with these events during hospitalization are high. Several factors are known to influence treatment outcome, including lifestyle factors (for instance smoking or co-medication) but also genetic factors. The field of pharmacogenomics investigates the relation between genetic variation and treatment outcome. For several medicine-gene combination there is clear link between the presence of genetic variants in the gene and the development of adverse drug reactions. For those gene-medicine combinations guidelines have been developed for use in the clinical setting to optimise treatment outcome. However, all aspects to the genetic bases of ADRs is still not known or not investigated for many medicines. Therefore we plan to use the UK biobank to further expand our knowledge on the genetic basis of adverse drug reactions.
Last years, several studies identified pharmacogenetic variants linked to ADRs using genome-wide approaches. Most studies focussed on specific medicines linked to specific ADRs. The UK biobank is a perfect resources that allows us to combine medicines with similar working mechanisms. By combining medicines with the same working mechanisms we will have gain insight in the common genetic basis of ADRs for these specific medicines. We also believe that medicines with different working mechanisms might still result in the same ADRs due to factors that are not directly linked to medication processing in the body. E.g. medicines that can results in neuropathy might cause this due to an underlying genetic variant in genes that result in a neuropathy which will only come to light when there is an external trigger in this case a medicine. The UK biobank will also contain information on ADRs linked to these medicines with different working mechanisms that can lead to the same ADR. By investigating the latter we will gain insight whether ADRs linked to these (very) different medicines can be linked to common genetic dominators.
Project extension – April 2020
Besides adverse drug reactions we would like to extend the scope of the analysis to treatment response specifically for the treatment of pain and depression. Pain and anti-depressant treatment failure is often caused by lack of efficacy or exceedance of a patients tolerability of adverse drug reaction. We would like to explore if there are genetic variants causing pain or antidepressant treatment failure. Specifically for antidepressant treatment we would to see if these variants share the genetic underpinnings of major depressie disorders.
Last updated Apr 9, 2020