The effect of obesity on cardiovascular disease: mediation analysis with Mendelian randomization

Obesity is one of the most common health-threatening conditions in the world.

A particularly negative effect of obesity is the elevated risk of cardiovascular disease (CVD), which is the leading cause of death world-wide.

This effect is mediated through a wide range of biological mechanisms, but the relative importance of these mediators is not well understood. The overall aim of this cross-disciplinary project is to explore the mediating pathways from obesity to CVD.

We will develop novel statistical methods for mediation analysis, and use Mendelian randomization to protect against unmeasured confounding of the exposure, mediator and outcome. We will use the methods to analyze a large population-based cohort from the UK biobank. The proposed project is highly important, for several reasons.

By identifying the most influential mediators one can tailor treatments directly to these.

Also, learning about the mediating pathways from obesity to CVD is imperative for understanding the etiology of these conditions.

Finally, mediation analysis is one of the most important areas of modern epidemiological research; however, unmeasured confounding poses a constant threat to such analysis. Thus, the proposed project is expected to deliver novel statistical methods with a wide applicability in the field. The project will be carried out at the department of Medical Epidemiology and Biostatistics, Karolinska Institute.

The time frame is four years, divided evenly over four sub-projects.