Dr. Siobhan M. Dolan:“Direct to Consumer Genetic Testing: Are We Ready?”
Tuesday February 24th’s Social Medicine Rounds brought Dr. Siobhan Dolan to the Residency Program. Dr. Dolan is double-boarded (Obstetrics and Gynecology, Clinical Genetics) as well as having an MPH. She currently works in the Montefiore/AECOM clinical genetics testing service.
Dr. Dolan began by discussing the difference between traditional clinical genetics and the current field of genomics. Genetics was originally concerned with single gene defects, usually associated with rare diseases. These mutations were usually of high penetrance (i.e. having the genetic mutation usually caused you to be sick) and caused conditions (like Down’s syndrome) in which environment played a relatively minor role. Genomics, on the other hand, typically involves multiple (often interacting) genetic variants that are associated with common conditions. These genetic variants often confer only a modestly increased risk of the disease. The diseases in question are ones (such as lung cancer) in which the environment plays a large role. (For more on this distinction, see the article by Alan E. Guttmacher, M.D., and Francis S. Collins, M.D., Ph.D. in the November 7, 2002 issue of the New England Journal of Medicine entitled: Genomic Medicine: A Primer).
Genomic medicine promised to make genetics relevant to everyone. In a 1994 article in the American Journal of Human Genetics, Dr. Eric Hoffman predicted “[t]he day of the personal DNA profile provided at birth, complete with calculated risks of various cancers, heart disease, and many other conditions could be actuality by the time that current first-year medical students begin to practice medicine.” While this prediction proved premature, a few years later genomics entered the mass market with internet-based direct-to-consumer advertising.
Dr. Dolan expressed considerable skepticism regarding the value of many genetic tests. In order to assess their clinical validity she recommended use of the ACCE criteria developed by the Foundation for Blood Research for the CDC. These criteria evaluate:
- Analytic validity: Does the test actually measure the genetic variation it is supposed to measure? (“ability to accurately and reliably measure the genotype of interest. “)
- Clinical validity: Is the genetic variation actually predictive to the disorder of interest? (“ability to detect or predict the associated disorder (phenotype)”)
- Clinical utility: What are the risks and benefits of introducing the test into clinical practice?
- Ethical, Legal and Social Consequences of the Test
The ACCE criteria suggest 44 specific questions that should be answered in considering a given genetic test.
Several genetic tests have not lived up to their initial promise. For example, Roche’s AmpliChip CYP450 test was touted as a breakthrough that would allow individualized dosing, particularly of psychiatric medications. But the clinical utility of the test has been questioned (The Medical Letter, 47(1215/1216), August 15/29, 2005). In 2007 the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group writing in Genetics in Medicine concluded that: No evidence was available showing that the results of CYP450 testing influenced SSRI choice or dose and improved patient outcomes, or was useful in medical, personal, or public health decision-making.” [SSRI's are a common class of anti-depressant drugs].
Similar concerns have been raised about pharmacogenetic testing for warfarin. Reviewing commercial tests for CYP450 polymorphisms associated with differences in warfarin metabolism, The Medical Letter concluded in May of 2008 that: “Currently available data are probably insufficient to recommend pharmacogenetic testing just yet for all patients taking warfarin, but these tests may be helpful, especially in selecting an initial dose and in some patients with unexpected therapeutic responses to the drug. Whether they improve clinical outcomes remains to be established.” (The Medical Letter, 50(1286), May 19, 2008)
Regardless of these cautions genomics has now entered the world of direct to consumer advertising and Dr. Dolan reviewed the major categories of this fascinating “brave new world”. [Please note, we are not endorsing the use of any of these websites.]
1. Determining Paternity. DNA Lab Centers features a smiling baby on the home page with the caption: “Does he really have your eyes?” Results can be used to “provide Maternity, Paternity, Immigration, Grandparent and Sibling Testing/Verification.” The use of DNA for immigration cases is, apparently, a growing field.
2. Sites like Ancestry.com offer genetic testing which purport to allow one to investigate ancestry.
3. Dating and Social Networking: Sites like Gene Partner and Scientific Match claim to match people based on genetics. Gene Partner bases its system on HLA matching and the site provides references to 11 scientific publications. Four of these were non-human studies and three of the studies are listed twice (ouch!). Of the remaining four studies three relate to female preferences for different male odors and only one associates HLA types with romantic involvement, a study involving 48 couples. Not a particularly strong evidence base. Scientific Match seems also to use the HLA types, but the site is less explicit.
4. Sites looking for specific medical disorders: Sites like DNA Direct and 23 and me provide comprehensive genetic testing services include whole genome tests. Again, the clinical utility of most of these tests has yet to be demonstrated.
It is a shame that the development of genomics in the United States is being left to the marketplace. The British are rightly proud of their National Institute for Health and Clinical Excellence (NICE) which evaluates new drugs and devices prior to their adoption by the National Health Service. NICE’s decisions has been controversial at times, but this is to be expected given the nature of the decisions it makes. The new Federal stimulus bill sets aside $ 1.1 billion dollars for effectiveness research. This is a welcome move and long overdue.
Concluding thoughts:
Maybe major histocompatibility genes truly explain romance. But in the market, let the buyer beware.
I prefer poetry and will close with the thoughts of Edmund Spenser:
Amoretti XXX: My Love is like to ice, and I to fire
My Love is like to ice, and I to fire:
How comes it then that this her cold so great
Is not dissolved through my so hot desire,
But harder grows the more I her entreat?
Or how comes it that my exceeding heat
Is not allayed by her heart-frozen cold,
But that I burn much more in boiling sweat,
And feel my flames augmented manifold?
What more miraculous thing may be told,
That fire, which all things melts, should harden ice,
And ice, which is congeal’d with senseless cold,
Should kindle fire by wonderful device?
Such is the power of love in gentle mind,
That it can alter all the course of kind.
Posted by: Matt Anderson, MD
The central thrust of our post was that the clinical utility of many DNA tests has not been validated. Unvalidated tests should probably not be available on the market, much less advertised to consumers over the Internet.
Using DNA to test genetic relationships is a well-accepted practice with defined standards.
Our listing of sites was meant to be illustrative of the range of options that are available on the Internet.
Matt Anderson, MD
If you are not endorsing any of the websites, then why do you have a link to each site? Would you include us in your next blog about direct consumer purchase of DNA tests. We offer a very useful product to a population that wants to know the truth about paternity (and other family relationships) and take responsibility for their actions without state or federal involvement. Paternity and other family relationships are a very private matter in certain societies. Having the ability to come into a private, non-judgmental atmosphere to remove doubt provides Peace of Mind to many of our customers.