Human Integrative Physiology:  The Missing Link in Systems Biology?
Sponsored by the APS Physiological Genomics Group

Many genomic studies in humans can be broadly described as “association studies.” In these studies a genetic variant or collection of variants are tested for association with the presence or absence of a given phenotype in a population. Causal mechanistic insight into concepts from these associations is frequently gained from “expression” studies in isolated cells or animal models. In this context, there is limited information about how genetic variation in key regulatory pathways influences intermediate physiological responses that contribute to generating phenotypes of interest over time.  In this symposium we discuss these general concepts and propose that proper application of the “lost arts” of integrative physiology to humans with selected genetic variants can link genetic variation to the emergence of complex phenotypes via changes in physiological regulation. Additionally, we discuss the idea that when experiments are designed, the inherent power of integrative physiology techniques needs to be carefully balanced with current concepts about population genetics that typically guide association studies.