Significant common environmental effects on leukocyte subpopulations

Major efforts are invested in the analysis of phenotypic variation in a population of individuals. While many of these studies focus on the genetic basis of phenotypic variation via measurements of DNA polymorphic sites, the environmental effects are still elusive. Here we propose a methodology, called CCCE ('Cell Composition Common Environment'), to identify environmental effects on the composition of immune cell functionalities. Specifically, CCCE is focused on the common experiences that are shared between siblings (the ‘common environment’), designed to correct for cell subpopulation heterogeneity, and is based on a multicolor flow cytometry analysis across a large cohort of human monozygotic and dizygotic twins. We demonstrate that the CCCE methodology can provide insights on the relations between common environmental effects and the heterogenic functions of several immune cell types, such as NK cells effector functions and coagulation-related capabilities of monocytes. The software described in this article is available at http://csgi.tau.ac.il/CCCE.