Yesterday I wrote about the false Family History vs. Personal Genetics battle, today I look at the old chestnut of traditional risk factors. There seems to be a lot of fear among some professions that personal genetics is attempting to take over their jobs – it’s been like this from the beginning mainly due to misunderstanding (wilful or otherwise) exactly what personal genetics is and what it’s role in healthcare can be.
The latest salvo is from the EGAPP Working group who published their assessment of genetics vs. traditional risk factors (TRF) in cardiovascular disease risk. They looked at the 9p21 variant as well as 57 other variants in 28 genes associated with CVD and they sought to document
“the extent to which genomic profiling alters CVD risk estimation, alone and in combination with traditional risk factors, and the extent to which risk reclassification improves health outcomes”.Some conclusions from EGAPP:
- The magnitude of net health benefit from use of any of these tests alone or in combination is negligible.
- The EWG discourages clinical use unless further evidence supports improved clinical outcomes.
- the overall certainty of net health benefit is deemed “Low.”
- the estimated additional benefit from adding genomic markers to traditional risk factors was found to be negligible.
- Traditional risk factors such as those used in the Framingham Risk Scores have an advantage in clinical screening and risk assessment strategies because they measure the actual targets for therapy
- To add value, genomic testing should lead to better outcomes than those achievable by assessment and treatment of traditional risk factors alone.
- To be useful, genomic testing should provide demonstrable improvement on the predictive value of TRFs.
Fine, fine, fine, all correct and proven, but all missing the point completely. It does not matter that the genetics did not add anything, even with the legendary 9p21 variant. Why should personal genetics be thought of as a replacement for traditional risk factors? EGAPP in it’s narrow scope is correct, but as usual the “negligible benefits” etc. will be, actually are being, quoted widely to trivialise personal genetics, just as the family history study was used to consign genetics to irrelevance.
The world moves on and nothing changes. In the early days, almost 10 years ago, it was the same, the genetic risk had to be “over and above” traditional risk factors. But why? What is expected of genes, are they supposed to possess some transcendent quality so that some sort of independent risk factor emerges from a genetic profile? Or is it that genes code for proteins that function in the various pathways, the perturbation of which can lead to metabolic problems (the traditional risk factors) and eventually disease?
I get told off for car metaphors but here goes. Driving along in the rain, hit the brakes, skid, crash. Skidding is a risk factor for crashing, I can try to reverse the skid, it might work, but I would rather avoid it in the first place by driving better in the rain (at least until pharma comes up with the anti-lock brakes pill).
The aim of personal genetics is to prolong health. High blood pressure, low bone mineral density, arterial plaques, etc., are not present in healthy people. They might be useful indicators in predicting disease, they might be useful values to put into the Framingham calculator, but they are best avoided in the first place.
All this is obvious – so why is it that genetics is compared so frequently to classical risk factors? It’s not a surprise that they don’t contribute more, why should they? Genetic variation does not have this magic “over and above” quality. But it is there from birth, it is there even in healthy people. This was mentioned in an earlier influential paper comparing SNPs & risk factors in type 2 diabetes, the authors claimed that the genetics added little to nothing but did add as a by the way:
“Although genetic information appeared to be useful when only factors known in youth were considered, genetic information in the context of risk factors measured in adulthood did not help to refine the prediction of diabetes risk” (Meigs et al)
So it was only useful in youth, in healthy people. Dammit. When people are actually ill the traditional risk factors win hands down. Of course. So the contribution of genetics is “negligible”. No use for genetics in healthcare yet.
But what about the poor healthy people who want to stay that way? No family history for anything I particular. Normal BMI, fat mass, lipids, blood pressure, glucose, insulin, HbA1c, and so on… Will regular medicine and TRF testing still win? No, it can’t. I’m not saying that genetics will definitely win, but it’s certainly favourite, at least it has the possibility of scoring where regular medicine does not.
EGAPP is probably correct, not ready for use in the clinic – at least not in the clinics that most of us are familiar with. But this is not the same as not ready for use. Most doctors I have spoken to (many) want genetics to be a simple test that classifies risk; high, medium or low, and tells them what to do. This is a reasonable desire and fits in with the way most of them work – a few minutes per patient, clear decision making advice required. They have no time for a long interpretation and explanation of small risk changes, up or down, how to ameliorate raised risks in the long term through diet & lifestyle, etc. It’s not their job, mostly. But if “CVD is a public health care concern” (EGAPP) it needs a public health care approach and if genetics is going to be involved it will not be as a replacement for conventional risk factors but will be incorporated into healthcare long before conventional risk factors even begin to raise their ugly heads.
This is where the research should be going: proper assessments of personal genetics vs. standard health information with healthy people. Is genetics better than classical risk factors in healthy people? (of course this is just the same as asking “is genetics better than NOTHING” – which is exactly the right question). I’m expecting that 23andme will be exploring just this – they have the money, the skills, the database and the experience, and of course some business interest (as everybody does, including MDs and clinical geneticists). But I hope EGAPP will do it too.
It’s not genetics vs. regular healthcare, it’s when, where and how to use genetics in healthcare.
PS – The PHG foundation has a nice report on the Genetics and Public Policy Centre survey.
Early days, these were early adopters driven by some reason to take the tests, but a promising start.
“A random sample of 1,048 US customers of the three major companies offering personal genomics DTC (23andMe, deCODEme and Navigenics) were surveyed online between June 2009 and March 2010…58% said they learned information that would help improve their health, and as a result of testing, 34% said they were being more careful about their diet and 14% were exercising more…This study provides long-overdue evidence that consumers are satisfied with DTC genetic testing services, and are generally able to interpret their results. It also indicates that there may be direct health benefits resulting from the tests in terms of behaviour modification…this survey indicates not only the absence of harm caused by DTC genetic testing services, but also the possibility of benefits.”
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2010). Recommendations from the EGAPP Working Group: Genomic profiling to assess cardiovascular risk to improve cardiovascular health. Genetics in medicine : official journal of the American College of Medical Genetics PMID: 21042222