The impact of new research technologies on our understanding of environmental causes of disease: the concept of clinical vulnerability

We are still far from completely understanding the etiology and causal patterns for many common diseases, such as breast and colon cancer, or neurodegenerative diseases. In spite of decades of epidemiological research, the etiology of many such conditions is still largely unknown.For a long time it has been hypothesized that most chronic diseases have an environmental origin (using the term "environment" in a broad sense, to indicate essentially what is not due to genetic predisposition). This claim was based on descriptive data showing the broad range of incidence rates in different parts of the world, the rapid temporal changes - such as those currently occurring in China and India - and the crucial observation of incidence rates in migrant populations. The latter unequivocally showed that migrants rapidly acquire - sometimes already in the first generation after migration - the risk of disease that is typical of the population where they move.However, "environmental" risks have been largely elusive in epidemiological research, and there is still much debate on the real impact of the environment, whose role tends to be overshadowed in recent times by the successes of genetics, in particular Genome-wide association studies (GWAS). Clearly, we need a disease model that allows us to encompass both the mass of genetic data coming from GWAS and the still elusive role of many environmental exposures.The technological revolution in genetics, which in 2007-2009 led to the identification of a number of novel genes for several common diseases, is inspiring but at the same time a little disappointing. Most highly-penetrant genes had already been uncovered by linkage studies, so that "genome-wide scans" could mainly identify low-penetrant genes. It is a fact that - with a few exceptions - what has been found is genetic variants weakly associated with chronic diseases, with relative risks of 1.15-1.5. These risks are much lower than some known environmental exposures, and of t