Friday, October 3, 2014

An example of the problem of risk projection

One of the biggest problems in biomedical, including genomic, disease risk prediction is that it is almost always based on projections of past risks into the future. We wrote about that the other day (here), but here's yet another example--and they abound.

Baby swimming; Wikipedia

The Oct 1 NYTimes had a story about a boom in pre-school fitness programs.  If parents, and it will largely be middle-class privileged parents, adopt this fad, it may have long-term, even lifelong, implications for the future health of the kids who partake.  If the Times is right that this is a boom industry, one can imagine a whole generation of super healthy upper and upper middle class future adults in the making.  That would be quite good (unless, of course, it turns out that various muscle, skeletal, or other traits are harmed by overdoing this early exercise), and so a beneficial practice for individual and public health.

But, even if they are healthier than today's adults, eventually these babies will develop diseases as they grow older.  From our perspective as scientists who think about pitfalls to doing science, this raises some potential problems for future researchers doing disease genetics or environmental epidemiology, looking for risk factors associated with disease.
1.  If it's predominantly parents of a given ancestry, European urbanites say, who enroll their kids, this can induce false positive genomic signals.  Any other kind of clustering related to who enrolls can be equally problematic; 
2.  The kids themselves may not remember, or investigators decades from now may not be aware of these early fitness programs even to ask about them.  The exposure to such programs' effects may as a result go under-reported in epidemiological or genetic association studies, leading to distorted estimates of other risk factors; 
3.  If  parents who enroll their kids are, as seems likely, themselves into fitness plans, there can be a family association of altered risk with genotype that will be challenging to identify and correct for as they could seem to be genetic; 
4.  If the kids are inculcated with other health-habits, based on today's do-this/don't-do-that fashions (e.g., here's a story in the Times about 6 year olds choosing to be vegan), there will be correlations with later disease that will not necessarily be identifiable, and indeed, it may be the parents' attitudes that are responsible, not the kids' genotypes or behavioral choices freely made.
Our society already spends much media ink and research resources in hyping risk estimates for genes and lifestyle factors alike, that are made retrospectively based on the behavioral and exposure antecedents of today's disease cases, as ascertained by means such as interview questionnaires (Did you smoke?  How much, for how long?  Did you get exercise when you were a child?  How much, for how long? How many eggs did you eat per week when you were in your twenties?). Those are not only quite inaccurate, involving things occurring decades ago, but the chronic, complex disease risks we're exposed to today generally won't materialize for decades into the future.  Indeed, if we read about a risky behavior or food, this makes a lot of us change our behavior, yet another complication--and one which operates regularly as we read advice from the latest research, not always aware of its potential weaknesses.

So risk estimates are about the future, but future exposures can't even in principle be known.   This is obvious, so why is awareness of the problem so low?  And what, if anything, can we do about it besides discounting risk estimates and acknowledging that they usually have unknown precision?


Ken Weiss said...

Yes, here we also have risk factors that are not predictable as well as exposure levels. It may not even make sense to think of these in terms of 'probabilities' or 'amounts' of exposure. Ultimately mathematics may be able in principle to account for everything, but in practice this simply isn't the case--meaning that the elegance and convenience of mathematical (or probabilistic) risk modeling is nice for professors but often rather irrelevant.

Sometimes, of course, it works very well and therein lies a big challenge--when, where, and how well will that be?

Anne Buchanan said...

It's interesting to see the hubris with which we in rich countries are talking about Ebola and the impossibility of it spreading here -- we are scientists, we have scientific knowledge about how to prevent the spread, thus it will be prevented. The Texas case, just a single case, shows how wide the gap between knowledge and practice can be.

Ken Weiss said...

Yes, and the doughboys will be home before Christmas. And BSE won't actually spread to humans. And ISIS will fold its tent and go away. And California's water problem--not to worry! We'll install some windmills (after we've pumped out all the natural gas and oil we want to burn). And in case we exterminate species we want, we'll even, we're told, reconstruct them from DNA.

Anne Buchanan said...

Hey, these are all problems that science can solve, right?