Too Much Information

In a recent JAMA paper on whole genome sequencing the authors examine 12 patients in detail and the results were mixed. One patient had BRCA mutation which was beneficial. The others were a mixed bag.

As the authors conclude:  

In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine.

The problem is several fold. First there are many know genes with uncertain effects. Second there are many unknown genes with totally uncertain effects. Yes the genome has been mapped for over a decade but the unknow genes are "known" but their effects are uncertain. Third there are many epigenetic effects which are uncertain. Fourth many cancers are the result of subtle in lesion changes not reflective of a large scale sample.

The authors continue:  

As technical barriers to human DNA sequencing decrease and the cost of whole-genome sequencing (WGS) approaches $1000, WGS and protein-coding genome sequencing (whole-exome sequencing [WES]) are increasingly used in clinical medicine. Both WGS/WES can successfully aid clinical diagnosis, reveal the genetic basis of rare familial diseases, and explicate novel disease biology^. Regardless of context, even in apparently healthy individuals, WGS/WES are expected to uncover genetic findings of potential clinical importance. However, comprehensive clinical interpretation and reporting of clinically significant findings are seldom performed. As WGS/WES are applied more broadly, questions have been raised about the duty for discovery, interpretation, and reporting of clinical findings. Recently published recommendations define genetic variant types in a minimum list of inherited disease genes that are suggested to be subject to discovery, reporting, and clinical follow-up regardless of the primary indication for sequencing, patient preference, or patient age. Despite this, the technical sensitivity and reproducibility of clinical genetic findings using WGS and the clinical opportunities and costs associated with discovery and reporting of these and other clinical findings in WGS data remain undefined.

 The problems that can be seen is that many patients may demand the tests or physicians can see a way to "sell" the tests and the result will be an added load on the already burdened Health Care system to deal with what is at best conjecture. One wonders how this fits into the ACA?