Monday, April 6, 2009

Family History beats fancy Genetic Test! Again!

I was talking to the president elect of the ACMG the other day about something that could be pretty useful. I told him that even though we disagree about the role of DTC, I laud his efforts towards education.

Our teaching point should be plain and simple. The family history is the best addition to the geneticist's history and physical. It separates them from other specialities. It is a help towards clinical judgement and use of testing. This is precisely the thing that will keep geneticists from being replaced by eager self-testers and Online "web apps" to teach patients about their 6 billion base pair report.

In genetics we all know of benign variants in genes and hell, even chromosomes. Changes which in the grand scheme of things may never make a difference......that's because clinical always trumps basic science.

I was presenting with Aidan Power on Friday at Yale, when a "entrepreneur" said, "My friend a cardiologist from Cornell says that there are 'validated' markers for heart disease that no doctors are using." I told her that most "validated" biomarkers often add very little to the predictive abilities and algorithms we already have as clinicians.

I then mentioned the case with 9p21.3 where it adds absolutely no information to risk prediction when compared to framingham risk.....But is highly statistically significant for association with MI. So the statistically bamboozled non-clinician thinks that this is an amazing tool, while the physician sees this for what it is, useless information to help them predict disease risk, which is why I keep hating on these SNP chip testing companies.......They make science the lead, rather than the clinical utility.......which inevtiably will produce genohype! But I can't blame the two undergrads in Mountain View. Neither of them are clinicians......unlike Agus and Vanier.......

That being said, there is one thing that does add quite a bit.......Family History. Now in another, "Of course it does" moment a study from the home of Factor V Leiden

People used to use Factor V testing all the time. Now it has fallen out of favor. Even so you can see that sites such as DNADirect still offer it. Why? Who knows, maybe they don't follow the hematology literature so well......

From the study:

Frits R. Rosendaal, M.D., Ph.D., of Leiden University, and colleagues reported in the March 23 issue of Archives of Internal Medicine.
The risk quadrupled when family history included more than one affected member, and the relative risk soared to 64 with a positive family history and a genetic or environmental risk factor versus no family history or other factors.

Investigators found that 505 patients (31.5%) and 375 controls (17.3%) reported one or more first-degree relatives with a history of VTE. The difference translated into an odds ratio of 2.2 (95% CI 1.9 to 2.6). The association was stronger when only family members who had venous thrombosis before age 50 years were considered positive (OR 2.7, 95% CI 2.2 to 3.4) or when several relatives were affected (OR 3.9, 95% CI 2.7 to 5.7). The OR for venous thrombosis when several relatives were affected, at least one of them before age 50 years, was 4.4 (95% CI 2.8 to 6.9).

It sounds like we have some more clinical criteria which remains WAYYYYYY better than a Factor V Leiden gene test.
From the study.....
"Environmental risk factors together with a positive family history strongly increase the risk of venous thrombosis. In the absence of a known genetic risk factor, the risk is already increased more than 15-fold. Genetic testing to identify additional risk would then not seem useful."

The Sherpa Says: In another study, which will not be splashed all over the WSJ and NYT, we find, Family history has more power than gene tests.........

1 comment:

Rebecca Taylor said...

I used to perform the test for FVL in a clinical molecular lab. Once we gave out a false positive result for a patient who had a benign polymorphism one base pair upstream from from the FVL mutation. When we called the Doc to correct the report, he didn't even know that he had ordered the test. (it was obviously part of some standard panel) Moreover he didn't even know what the clinical implications were. Clearly the FVL test really wasn't all that important.

After working both in research and clinical genetics labs, I now understand how important a clinical history is. The majority of the tests we performed in the clinical lab were simply one piece of a much larger puzzle and every report we put out said that our results were no substitute for clinical findings.

So, from someone who churns out genetic test results everyday, thank-you Dr. Murphy for being there to remind us that a genetic test isn't everything. A patient is much more than just a series of SNPs.