4 posts tagged with "colocalization"

Complex traits like blood pressure (BP) and body mass index (BMI) are highly polygenic: hundreds of associated variants can be used as instruments in Mendelian randomization (MR). But those variants don’t all “mean the same thing” biologically—some may act through kidney physiology, others through vasculature, neurobiology, metabolism, and so on. If we can separate instruments into interpretable biological subsets, we can start asking questions like:

• Which component of BP is most responsible for coronary heart disease risk?
• Are BMI → atrial fibrillation effects more “metabolic” or more “neuro-behavioural”?

Work led by Genevieve Leyden and Maria Sobczyk and now published in Genome Medicine sets out to do exactly this by comparing two ways of partitioning genetic instruments before running MR.

Overview​

Genetic studies have been very biased towards populations of European ancestry in western Europe and the United States of America, and this has led to a significant bias in the application of Mendelian randomization (MR) to identify intervention targets. In this project we worked with a leading international genetics consortium, the Global Biobank Meta-analysis Initiative (GBMI) to evaluate the differences in predicted drug target effects between African and European ancestry populations.

Overview​

This short animation explains how we use Mendelian randomization and colocalization to help prioritise drug targets. One of our aims in both  programme 4 of the MRC IEU and the Integrative Cancer Epidemiology Programme is to integrate such prioritizations with other data to help inform drug development.

Overview​