Genetic diagnosis, treatment, monitoring, and surveillance

Idea: Genetic analysis has begun to identify genetic risk factors. We need to consider the social infrastructure needed to keep track of the genetic and environmental exposures with a view to useful epidemiological analysis and subsequent healthcare measures. Even in cases where the condition has a clear-cut link to a single changed gene and treatment is possible, there is complexity in sustaining that treatment.

For a few years this decade, genome-wide association studies seemed to hold promise for detecting genes related to diseases and for the invention of drug-based treatments.

But, 18 months ago, , A Genetics Company Fails, Its Research Too Complex

In 2009, Khoury et al. were concerned that the promises were not over-stated. Look at the table giving their quality control proposal.

In 2005, Frank cautions that epidemiology needs as much data about environmental factors as genes, but observes that the playing field is not level. (Give credit of you ever cite this powerpoint.)

Even for (rare) diseases governed by single genes, the path from genetic diagnosis to therapy is complicated as the poster-child case of PKU shows. From Taylor (2009):

  • Diane Paul’s (1998) history of PKU screening describes, the certainty of severe retardation has been replaced by a chronic disease with a new set of problems. Screening of newborns became routine quite rapidly during the 1960s and 70s, but there remains an ongoing struggle in the USA to secure health insurance coverage for the special diet and to enlist family and peers to support PKU individuals staying on that diet through adolescence and into adulthood. For women who do not maintain the diet well and become pregnant, high levels of phenylalanine adversely affect the development of their non-PKU fetuses. This so-called maternal PKU is a public health concern that did not previously exist. In short, a more complex picture of development in a social environment is needed for anyone to make use of the knowledge that the fate of individuals with the PKU gene is not determined at birth.

Genetic analysis

This post’s readings deal with analysis of actual genes, whereas most of the previous post’s readings about heritability looked at variation in some observed trait. With the expanding role of genetic analysis comes the challenge of how to fit this into our healthcare system. Genetic risk factors associated with common diseases, individually may only have a weak risk-ratio, but combinations of these factors may, researchers hope, have a larger impact of the population.
Khoury et al try to make a case for establishing standards for “presenting and interpreting cumulative evidence on gene-disease associations.” They describe problems such as publication and selection biases, differences in collection and analysis of samples and the presence of undetected gene-environment interactions among studies of genome-wide analysis. This has lead to a high incidence of type 1 errors in GWA studies (false positives). Networks are attempting to establish consensus guidelines for reporting and publishing gene-disease associations to reduce this risk. (Do a web search to see how things have developed in the two years since.)
Bowcock describes how a consortium of 50 British groups examined genetic variance in a genome-wide association study. They examined the genetic issues for 7 common diseases including RA, CAD, bipolar disorders, diabetes, hypertension and Crohn’s disease. To identify the genetic risk factors for these common diseases, they examined 500,000 genetic markers(or SNPs-single nucleotide polymorphisms) from the genomes of 17,000 individuals. They found very little difference between controls and cases, but they did find some SNPs that can be considered genetic risk factors for a particular disease, some confirming previous studies, but others identifying unique genes that affect susceptibility to a disease.
The more advanced the genetic analysis becomes, the issue of how this information is going to be utilized for the treatment or monitoring of a person’s risk for disease and what part prevention and screening plays in the individual’s health status presents itself. Bowcock cautions that translating someone’s risk into “medical practice” should not be done without “larger patient populations, well-annotated clinical databases and sophisticated environmental assessment.”
Frank’s powerpoints remind us that knowledge about environmental factors is needed as well, but because it costs more to collect and store, it tends not to be collected. This will make some epi. research questions impossible to address and shape the kinds of knowledge that can be put into biomedical practice and social policy.

Social application of knowledge about genes
The Paul article gives us an example of how a rare genetic disorder, Phenylketonuria (PKU) has been managed. Even though the incidence is between 1 in 11,000 and 1 in 15,000 births, all newborns are tested for it in the US, Canada, Australia, New Zealand, Japan and most other Western and Eastern European countries. The article chronicles the history of instituting the screening procedures for PKU. PKU was described as a “treatable genetic disease.” If left untreated, it results in severe mental retardation and behavioral abnormalities. PKU can be treated by a special diet which eliminates phenylalanine toxicity in the blood of those with PKU. There were policy issues involved in the PKU screening process that warrant examination. What were the societal factors that contributed to the federal initiative in the US in 1961? Not everyone was a proponent of the testing of every newborn for such a rare genetic disease. Problems of treatment efficacy and the question of the “cost” of the program are also addressed.
As we become more advanced in genetic analysis, many similar issues may be encountered for other conditions. One current related topic is the role of BRCA1 and BRAC2 inherited breast cancer gene abnormalities. Although they only account for about 10% of all breast cancers, there is much discussion about the Pros and Cons of seeking your genetic profile for breast cancer. Issues of prophylactic breast removal surgery, discrimination by health insurers and stress and anxiety associated with knowing your genetic profile are all ones that can be related to other genetic testing.
Taylor (2009) looks in broad brush at the overall project of application of genetic information.

(This post continues a series laying out a sequence of basic ideas in thinking like epidemiologists, especially epidemiologists who pay attention to possible social influences on the development and unequal distribution of diseases and behaviors in populations [see first post in series and contribute to open-source curriculum].)


Bowcock, A. M. (2007). “Guilt by association.” Nature 447: 645-646.
Frank, J. (2005). “A Tale of (More Than ?) Two Cohorts – from Canada.” 3rd International Conference on Developmental Origins of Health and Disease.
Khoury, M. J., J. Little, M. Gwinn and J. P. Ioannidis (2007). “On the synthesis and interpretation of consistent but weak gene-disease associations in the era of genome-wide association studies.” International Journal of Epidemiology 36: 439-445.
Paul, D. (1998). The history of newborn phenylketonuria screening in the U.S. Final Report of the Task on Genetic Testing. Baltimore, Johns Hopkins University Press: 1-13.
Taylor, P. J. (2009). “Infrastructure and Scaffolding: Interpretation and Change of Research Involving Human Genetic Information.” Science as Culture, 18(4):435-459.


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