A systematic approach to multifactorial cardiovascular disease: causal analysis.

The combination of systems biology and large data sets offers new approaches to the study of cardiovascular diseases. These new approaches are especially important for the common cardiovascular diseases that have long been described as multifactorial. This promise is undermined by biologists' skepticism of the spider web-like network diagrams required to analyze these large data sets. Although these spider webs resemble composites of the familiar biochemical pathway diagrams, the complexity of the webs is overwhelming. As a result, biologists collaborate with data analysts whose mathematical methods seem much like those of experts using Ouija boards. To make matters worse, it is not evident how to design experiments when the network implies that many molecules must be part of the disease process. Our goal is to remove some of this mystery and suggest a simple experimental approach to the design of experiments appropriate for such analysis. We will attempt to explain how combinations of data sets that include all possible variables, graphical diagrams, complementation of different data sets, and Bayesian analyses now make it possible to determine the causes of multifactorial cardiovascular disease. We will describe this approach using the term causal analysis. Finally, we will describe how causal analysis is already being used to decipher the interactions among cytokines as causes of cardiovascular disease.