1. Genetic Medicine
  2. AJHG is in and my

AJHG is in and my Favorite Muin is in it! But He Is NOT the Father!

Posted on by



"With breast cancer as an example, we examined the combined effect of uncertainties in population incidence rates, genotype frequency, effect sizes, and models of joint effects among genetic variants on lifetime risk estimates. We performed simulations to estimate lifetime breast cancer risk for carriers and noncarriers of genetic variants. We derived population-based cancer incidence rates from Surveillance, Epidemiology, and End Results (SEER) Program and comparative international data. We used data for non-Hispanic white women from 2003 to 2005. We derived genotype frequencies and effect sizes from published GWAS and meta-analyses. For a single genetic variant in FGFR2 gene (rs2981582), combination of uncertainty in these parameters produced risk estimates where upper and lower 95% simulation intervals differed by more than 3-fold. "


Did you get that?

They took a look at what it really means to give point estimates for lifetime risk of disease comparing with population risk data. In this case they chose breast cancer.......and FGFR2

Their conclusion?

Epidemiologic parameters involved in computation of disease risk have substantial uncertainty, and cumulative uncertainty should be properly recognized. Reliance on point estimates alone could be seriously misleading.

Do you get what they are saying? Let me break it down this way. When I see a patient for BRCA testing they always ask

"How high is my risk?"

I say: "Well.......it is a range."

Most people don't like ranges. In our little rat brains we think a range means uncertainty and probably a little guessing. Most patients don't like to go to doctors who give ranges or guesses.

Nor do people like buying things that don't give them "exacts" People very often, when left to their own devices would choose black and white over gray. They just don't like feeling uncertain.

That's precisely the big problem with how genetic testing has been marketed.

Think about it.



On 23andMe: Find your Norovirus resistance!!

OR


Sounds pretty certain to me.....

Do you get it?

Well, the answer is simple. Nothing in life is certain. Nothing, except death and taxes.

This study shows that if your model relies on too many uncertainties, your risk model fails. This is the biggest problem with the DTC Genomics companies' models. They are based on too much uncertainty and as such fall in the realm of fortune teller rather than risk prognosticator.

This is precisely why I have said "Data is Data, but Data can be Garbage."

And Garbage In = Garbage Out.

The Sherpa Says: with any risk model there is uncertainty, no surprise there. But the real surprise is the marketing of it as CERTAINTY to an unsuspecting and primed for certainty public.
Related Posts

Comments are closed.


  1. Genetic Medicine
  2. AJHG is in and my