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.........

American Society of Human Genetics speaks out on DTC testing

After a wonderful conference call with some friends regarding the future of personal genomes, I was heartened to see ASHG put out a statement on Direct To Consumer (DTC) testing. Here is what these learned individuals say.

Currently, DTC genetic testing is permitted in about half the
states2 and is subject to little oversight at the federal level. In July
2006, the Government Accountability Office issued a report documenting
troubling marketing practices by some DTC testing
companies,3 and the Federal Trade Commission (FTC) issued a
consumer alert cautioning consumers to be skeptical about claims
made by some DTC companies

While DTC testing also encompasses paternity and ancestry testing,
this policy statement addresses solely those genetic tests that
make health-related claims or that directly affect health care decision
making.

For a test to be of good quality,
the laboratory performing it must be able to obtain the correct
answer reliably, meaning that it detects a particular genetic variant
when it is present and does not detect the variant when it
is absent. A test’s accuracy is referred to as “analytic validity.”
Further, there must be adequate scientific evidence to support the
correlation between the genetic variant and a particular health
condition or risk—the so-called clinical validity.

Currently, the federal government exercises limited oversight
of the analytic validity of genetic tests and virtually no oversight
of their clinical validity.

Several complaints have been filed and
are pending with the FTC about a specific DTC genetic-testing
company, and the FTC recently issued a consumer alert warning
the public that “some of these [DTC] tests lack scientific validity,
and others provide medical results that are meaningful only in
the context of a full medical evaluation.”

So there in lies the problem. They have several solutions.

Recommendations
I. Transparency
To promote transparency and to permit providers and consumers to
make informed decisions about DTC genetic testing, companies must
provide all relevant information about offered tests in a readily accessible
and understandable manner.

a. Companies offering DTC genetic testing should disclose the
sensitivity, specificity, and predictive value of the test, and the
populations for which this information is known, in a readily
understandable and accessible fashion.

b. Companies offering DTC testing should disclose the strength
of scientific evidence on which any claims of benefit are based,
as well as any limitations to the claimed benefits. For example,
if a disease or condition may be caused by many factors, including
the presence of a particular genetic variant, the company
should disclose that other factors may cause the condition
and that absence of the variant does not mean the
patient is not at risk for the disease.

c. Companies offering DTC testing should clearly disclose all risks
associated with testing, including psychological risks and risks
to family members.

d. Companies offering DTC testing should disclose the CLIA
certification status of the laboratory performing the genetic
testing.

e. Companies offering DTC testing should maintain the privacy
of all genetic information and disclose their privacy policies,
including whether they comply with HIPAA.

f. Companies offering DTC testing and making lifestyle, nutritional,
pharmacologic, or other treatment recommendations
on the basis of the results of those tests should disclose the
clinical evidence for and against the efficacy of such interventions,
with respect to those specific recommendations
and indications.

The Sherpa Says:

I am still waiting for the data from Salugen/Luxor...........hmmm I wonder why? Wake up people, this field is filled with snake oil salesmen!!!!

TCF7L2 Strikes again, This time it's the Finns

The Latest edition of Mendel's Garden is up at Scienceroll. If you haven't seen it, the Gregorian Rap All-Stars video is a must see!

It's official. I can say without any doubt that the gene TCF7L2 is somehow implicated in diabetes. Another whole genome association study was performed and results were published in the American Journal of Human Genetics.

The study which performed because there only exist a handful of genes that have been implicated in the genetics of diabetes. These include PPAR gamma, TCF7L2, KCNJ11, CPN10, FTO. And because GWAS is hot now. They selected 4 populations, all Caucasian. 200 Finns with diabetes and 200 without, similar numbers of Ashkenazi Jews, 100 soccer hooligans from Manchester and 99 affected Brits, as well as 100 Germans with diabetes and another 100 without.

What they found was not surprising. TCF7L2 SNPs rs7903146, rs7901695 and rs122255372 were all replicated as linked again with ORs of 1.6-1.7. They also found several candidate loci. None which were that impressive when attempted to be replicated.

So, what does this all mean? Well it means that there is an increased risk for diabetes if you have any of the aforementioned changes in your TCF7L2 gene. But how does that help us? Now that it is shown to be linked, we need some data on how to prevent diabetes in the carriers of altered TCF7L2.

Does anyone have good data on this?

The Sherpa Says: Sometimes I do eat humble pie. That being said, I will not recommend TCF7L2 testing for anyone. Importantly because there are several SNPs associated, not just the SNP that deCode tests for. There is more to this diabetes story than meets the eye.