Francis Collins "upbeat" about impact of common disease genetics

Emily Singer has been doing a great job of covering the consumer genetics beat over at Technology Review; her most recent piece draws on a recent presentation by former head of the National Human Genome Research
Institute Francis Collins.

Collins caused a bit of a stir during his presentation (at last week's Consumer Genetics Show in Boston) by announcing that he had signed up for several personal genomics services under a false name. His conclusions:

Collins said that sequence-wise, the tests "appear to be
highly accurate": there were almost no differences in the genotype information generated
in the three different analyses. But there were significant differences in the
numbers of genetic variations used to calculate disease risk, as well as the final
risk score. For example, one company used 5 single nucleotide polymorphisms,
or SNPs, to calculate risk for a particular disease, pronouncing Collins at low
risk. Another used 10 SNPs, placing him at high risk, and the third used 15, concluding
that he is at average risk. Collins also said that the analyses provided little information
on his "carrier status," meaning whether he carried genetic risk factors that didn't
influence his own risk of disease but could be passed down to future
generations.

There's nothing particularly new here, except that these words come out the mouth of a science rock god. For instance, the high technical accuracy of these tests is unsurprising given that personal genomics companies rely on the same technology developed and painstakingly refined for use in massive genome-wide association studies.

The differences in risk prediction algorithms between companies is a chronic concern - the companies can even differ substantially in their estimates of the background risk of common diseases - that makes it difficult to compare results; there have been noises made about fixing these discrepancies for some time, but they persist. Finally, personal genomics companies (especially 23andMe and newcomer Pathway Genomics) currently provide some limited carrier testing, and stealthy outfit Counsyl appear to be aiming to provide a much more systematic assessment of carrier status.

Thus Collins' concerns about the performance of personal genomics companies seem to be technical and eminently soluble, rather than representing any deep ethical problems. That bodes well for personal genomics companies given Collins' high status within the ranks of science policy advisors to the current US administration (the rumours that he will become the next head of the National Institutes of Health are pervasive enough to have become boring).

Moving beyond consumer genomics, Collins's assessment of the impact of recent genome-wide association studies (GWAS) is optimistic - perhaps overly so:

"We have undervalued these studies," he said at the
Consumer Genetics Conference. "Even if a variant has a small impact on disease risk, that doesn't
mean it's not a good risk target." In type 2 diabetes, for example, two of the
nine common genetic variants that have so far been linked to the disease are
involved in the pathway targeted by two major diabetes drugs. "[Pharma
companies and others] have not jumped on this as rigorously as they could,"
said Collins. "Perhaps because it's a bit overwhelming--there are so many of
them."

GWAS signals certainly have the potential to teach us much about the underlying biology of common diseases, but it's important not to understate the barriers between finding association signals and designing effective therapeutics - especially given that we still don't understand the biological origins of the vast majority of GWAS hits.

It's good to see a likely future NIH head with such a bright vision for genomics, but I hope Collins' doesn't end up over-hyping the immediacy of the impact of genetics on healthcare. Such a move risks burning out the public before the real benefits of personalised medicine start to become readily apparent.

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