ent social and physical environments. This affected not only their life-span trajectories, fertility, health, and disease and survival rates, but also those of their children and grandchildren (see Chapter 5 for additional discussion). Thus information in the genome is inextricably linked with the cellular, physiological, psychological, social, and physical environments in which it functions over a lifetime, and many of these nongenetic factors are passed on to subsequent generations.

One of the limitations of a purely hierarchical perspective to integrating knowledge across levels is that, in reality, the effects of variation at any one level (e.g., gene, gene transcript, protein, metabolite, or tissue) are actually embedded in another level and are not simply “underneath” or “above” the other level. A well-established hierarchy is illustrated by the ways in which DNA is transcribed into messenger RNA, which is then translated into protein, which in turn is appropriately folded and chemically modified in order to perform a specific function in protein complexes. Conversely, an example of the complex, nonhierarchical, and embedded nature of biological information is the fact that some DNA variations affect transcription but are not found in the messenger RNA; other variants are transcribed and affect translation but are not found in the translated protein; and still others are transcribed, translated, and ultimately affect protein function. The following subsections further illustrate this concept and its implications for assessing the impact of associations and interactions among social, behavioral, and genetic factors on health.


The Human Genome Project and many other international efforts have been focused on understanding the nature of the genome and its variations. Millions of single nucleotide polymorphisms (SNPs) have been identified (e.g., see dbSNP from the National Center for Biotechnology Information1), and investigators around the world are engaged in performing genetic association studies in order to better understand the influences of these variations on measures of health and disease. It is well known that genetic variations within a gene can alter its expression both quantitatively and qualitatively. For example, mutations within the promoter region of a gene can influence when, where, and how much a particular gene is expressed (i.e., transcribed in messenger RNA). Currently, most gene expression studies ignore individual-level variation in gene expression due to genetic variation. However, over the past few years several landmark stud-

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