Pharmaceutical Sciences

G x E = ?

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The ExposomeThe technological and intellectual breakthroughs of the Human Genome Project (HGP) are changing the way we view health and medicine. The hope for new cures and treatments was palpable upon the completion of the HGP. But wait. Where are the promised cures?  Weren’t we told that they were just around the corner? Why aren’t the Genome-Wide Association Studies not identifying the genetic basis of every disease? Are we too impatient? I argue that it is more than just a matter of time. Relying solely on our genome to unravel disease causation will surely lead to disappointment. Why? Because there is more to life than our genes.

We know that the environment impacts our health. Pollution, nutrition, pharmaceutical and recreational drugs, physical activity, life stresses, climate, and other factors contribute to health and disease. Yet, we do not have a systematic plan to evaluate how these diverse components of our environment affect our health.

The concept of the exposome, which can be defined as the cumulative measure of environmental exposures and associated biological responses, included those from the diet, behavior, and endogenous processes, is poised to change this. While some have dismissed the exposome as one of the many misguided –omic adventures, the exposome is here to stay. One cannot conduct studies on gene-environment interactions without a measure of the environment. Currently, we can compare hundreds of thousands of SNPs to environmental measures such as smoking, work history, or geographical location.  Even with an occupational work history matrix that estimates what exposures may have occurred, we are still in dark ages when compared to the high resolution deep sequencing that is informing our genomic knowledge. Why can’t the environment be represented with the same gusto as our genome? This is what the exposome is all about. We need measures of our environmental exposures that are more sensitive, more comprehensive, and more widely accepted and recognized.

How can we possibly solve the equation G x E = X for any disease until we can actually have a value for E that is as robust as the value we have for G? The exposome has the potential to define the E variable in the equation, but only if the concept becomes a reality.  There have been a few recent research projects awarded in Europe and the US that are beginning to address this scientific deficit, but it is going to take more than dabbling in the science of the exposome. An international collaborative effort akin to the Human Genome Project will ultimately be necessary to provide the level of resolution needed to solve the puzzle.

The Exposome: A Primer was written to promote this idea. The text introduces the topic of the exposome, explains the need for this type of research, and provides some ideas for how to pursue such an undertaking. If you are interested in the importance of the environment in health and disease, you should read this book. If you aren’t interested in the role of the environment in health and disease, you should really read this book.

GaryMillerPhotoAbout Gary W. Miller

Gary W. Miller, PhD is the Asa Griggs Candler Professor of Environmental Health and Associate Dean for Research in the Rollins School of Public Health at Emory University.  He is Director of the HERCULES Exposome Research Center at Emory. His research interests include the role of environmental factors in Parkinson’s disease and the regulation of dopamine signaling in the brain. He is also Editor-in-Chief of Toxicological Sciences, the official journal of the Society of Toxicology.

To learn more about the Human Exposome Project, follow @exposome on Twitter or visit the website.

To learn more about the HERCULES Exposome Research Center at Emory University, follow @emoryhercules on Twitter or visit the website.

Dr. Miller’s book, The Exposome: A Primer, will publish in December 2013. It is the first book dedicated to exposomics, detailing the purpose and scope of this emerging field of study, its practical applications, and how it complements a broad range of disciplines. It is now available for pre-order.

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