Approved research

Using Mendelian randomization to evaluate the causal effect of disease related biomarkers on clinical outcomes

Lay summary

The aim with the proposed research is to use Mendelian randomization to evaluate the causal effect of biomarkers. In a Mendelian randomization study, a genetic variant is used as to divide a population into genotypic subgroups, in an analogous way as how participants are divided into arms in a randomized controlled trial. By dividing participants into subgroups with different genetically exposures to the biomarker, we can evaluate the causal effect of the biomarker on disease risk. The goal is to evaluate biomarkers that have been associated with cancers, immune- and cardiovascular diseases. Biomarkers are mainly used as indicator of diseases or to predict disease outcomes. The goal with the proposed research is to evaluate the biomarkers as direct risk factors of disease and thereby investigate their potential as drug targets. Genetic scores for a set of 35 biomarkers will be analysed for each biomarker separately. We will rely on previously identified (by us and others) genetic variants that have been identified to directly influence the levels of these biomarkers. Participants will be randomized into genetic subgroups, with different genetic levels of the biomarker, and compared with regards to relevant clinical events. For example biomarkers that have previously been associated with cancer should be analyzed in relation to cancer events and cardiovascular biomarkers in relation to cardiovascular events and measurements. We suggest using the full cohort in the analyses. In a first stage we want to analyse data for the participants that has been genotyped in the first batch. IN the second stage we want to analyse data for the remaining and/or the whole cohort.

The aim with the proposed research is to use Mendelian randomization to evaluate the causal effect of biomarkers. In a Mendelian randomization study, a genetic variant is used as to divide a population into genotypic subgroups, in an analogous way as how participants are divided into arms in a randomized controlled trial. By dividing participants into subgroups with different genetically exposures to the biomarker, we can evaluate the causal effect of the biomarker on disease risk. The goal is to evaluate biomarkers that have been associated with cancers, immune-  and cardiovascular diseases.

Scope extension: We would like to extend the scorpe to:

1) investigate the effect of rare varints on biomarkers

2) evaluate if rare varints can be used in Mendelian randomization to evaluate the causal effrect of biomakrers on disease risk