Developing cross-population Mendelian randomization for generalizing evidence on drug targets: the MRC Cross-Population Mendelian Randomization Network

The overarching aim of the MRC Cross-Population Mendelian Randomization Network is to integrate research expertise and resources across four MRC Units with expertise in cross-population genetic epidemiology to explore the use of Medelian randomization (MR) to evaluate generalisability of existing drugs and target drugs to specific sub-populations. The network will implement pilot studies focused on specific established drug targets (e.g. CETP, HMGCR) to investigate how differences in genetic architecture between populations affect estimates of efficacy. In parallel we will explore how differences in environmental interactions between populations (including public health policy such as folate supplementation) alter MR estimates of efficacy of such supplementation (using MTHFR as the instrument). The network will focus on the development of both cross-ancestry and ancestry-specific genetic instruments for MR and investigate how genetic colocalization with molecular targets (metabolomic, proteomic and transcriptomic) vary across populations.

The overarching aim of the MRC Cross-Population Mendelian Randomization Network is to integrate research expertise and resources across four MRC Units with expertise in cross-population genetic epidemiology to explore the use of Medelian randomization (MR) to evaluate generalisability of existing drugs and target drugs to specific sub-populations. The network will implement pilot studies focused on specific established drug targets (e.g. CETP, HMGCR) to investigate how differences in genetic architecture between populations affect estimates of efficacy. In parallel we will explore how differences in environmental interactions between populations (including public health policy such as folate supplementation) alter MR estimates of efficacy of such supplementation (using MTHFR as the instrument). The network will focus on the development of both cross-ancestry and ancestry-specific genetic instruments for MR and investigate how genetic colocalization with molecular targets (metabolomic, proteomic and transcriptomic) vary across populations.