Wednesday, December 5, 2012

Genes for response to head injury?

A story in Monday's New York Times tells of the kinds of long-term trauma that can result from the head injuries football or hockey players so often sustain throughout their careers.  This is a report of the posthumous study of 85 brains, all males, most of whom had been athletes, and most of whom suffered from some form of brain disease.
Of the group of 85 people, 80 percent (68 men) — nearly all of whom played sports — showed evidence of chronic traumatic encephalopathy, or C.T.E., a degenerative and incurable disease whose symptoms can include memory loss, depression and dementia.
The age range of the study group stretched from 17 to 98, which, the study authors report, meant that they could follow the course of the disease as it developed.  Symptoms ranged from mild headache and difficulty concentrating to severe dementia, aggression and difficulty finding words.

While this is a serious topic, and this study a good early effort at determining the effects of head injury, it can't be concluded from this study alone that head injuries cause C.T.E., nor can it be estimated what fraction of athletes or others susceptible to head injury are likely to develop brain disease, because the samples were all from people who had some obvious form of brain disease.  Some people apparently do suffer head trauma with no ill effects.

A prospective study of healthy athletes would be required to estimate the former, and the study would have to include a random sample of individuals who had sustained head injuries regardless of the health of their brain, to get even a ballpark estimate of the latter. That said, this and other studies of the connection between brain trauma and disease do lead to concern about the effects of fairly routine trauma. 

Let's GWAS it!!
However, because response to head injury does seem to vary we can envision that some geneticist somewhere will decide there must be genes that protect against unwanted consequences. The idea, one might fancy seeing, would be to use 'personalized genomic medicine' to identify who should perhaps play patty-cake instead of football, because s/he is vulnerable to C.T.E.s.  Or, the mapping result will send hundreds of otherwise-idea-free human geneticists off to find what gene in the identified chromosome regions makes the brain vulnerable to being shaken around, and to make hundreds of poor transgenic mice with mutations engineered in each of the genes to study the neurobiology.

Gene ontology and other omics communities will seize these seizure results as well.  The identified genes will be added to the repertoire of neural system genes--and their now-assumed neural function will be forced into this category if need be.  They'll be added to what's taught to med students, studies of dissected brains will be done on those who have the culprit variants, etc.

Of course, could it just be that the genetic basis of head trauma isn't related to neural variation at all?  It could be related to muscle strength or firing rate, or to eye-hand coordination, or respiratory factors yielding greater endurance, and so on.  That is, the correlation may have nothing to do with causation, just that variants that get you into high levels of sports will also get you into high levels of having your bell rung.

Or perhaps it's the result of dysfunctional parents, or parents of particular ethnic groups who don't have access to wealth and privilege, and who encourage their kids into sports as a way out of poverty?  Fish around in that community hard enough and you're sure to find some genes.  Maybe even genes for skin color, since African Americans tend to live in more poverty than European Americans, and tend therefore to be more into football.

Then, of course, will be the other set of genes, associated with being white and middle class, and having a soccer mom.

You can see where the assumption of genetic determinism can take one.....


JKW said...

I think you make some valid and important points. I do think there is quite a bit of high quality research being done in this area though. I find the evidence about the significance of beta amyloid loads in the brain (which could be modulated by a whole host of environmental factors- including traumatic injury and various enzymatic levels such as BACE1- in addition to genetic factors discussed in this paper) to be both compelling and worthy of more investigation. And I do believe there are some prospective studies of "healthy" adults (I recall seeing a few articles earlier this fall) that also are suggesting that beta amyloid may be more important than, say, just looking at someone's APOE4 status.

I guess I find the societal implications more interesting than the scientific questions right now - so what if we find "the causes" of CTE? I'm concerned about how the information would be applied (ad hoc by one individual or another and systematically by say the NCAA or the public school system). Should we start screening all kids for HCM, APOE4, ACTN3, Hb variants, etc? If so, at what time - birth, school attendance, varsity competition, some later age? And if we find carriers, what do we do then? Do we implement rules prohibiting them from playing any sports or relegating them to particular sports or positions that are considered "safer" for them? We simply can't bubblewrap the world for everyone and for every potential risk. Anyway, I'll save my other comments for the manuscript I'm in the midst of writing...

Ken Weiss said...

Your first points are fine, but I would say irrelevant to our point that mapping may find genes that are not directly related to head injuries but to what behaviorally or culturally puts someone at risk of head injuries.

Once you get injuries then perhaps one can do genetics of susceptibility, but why? One should have to show evidence that the genetic susceptibility is very great relative to the other factors that yield head injuries--including poverty that leads people to dangerous sports rather than law school, and things like that.

In other words, if we know the latter, then prevention could involve culture and be more effective than worrying about genes.

Of course, since we won't back off of the thrill of the head-bang, maybe we will have to do some testing, as you say. Will this involve civil rights issues? Can you be denied participation on the hockey team because of your genes?

Anyway, we were of course not making light of the head trauma, but only of the race to geneticize everything. Of course, that is what is going to be done, since that's the coin of the realm these days, in my opinion.

Ken Weiss said...

And, JKW, I will defend the idea that any genotype that, for whatever reason, gets people statistically to be more likely to play head-bashing sports, will likely show up in GWAS-like studies.

If the assumption is that this is related to neural function, we'll see intense efforts to figure out how. But if the actual 'cause' is something unrelated, that will be money down the drain.

So, it may be that black people are more likely to become boxers than others, because of their social circumstances and boxing being a perceived way out of poverty. Then pigmentation related genes would come under scrutiny as if melanin-production, for example, also serves neural function (and, I think it does).

So, you might say that everybody knows that skin color is a correlate but not a cause of boxing-related head injury. Maybe so, but how many other correlates-but-not-causes might there be that aren't so obvious?

JKW said...

Ah, I think I may have read your post too quickly and on too little sleep this morning. Yes, indeed, most of my points are irrelevant as to genetic "susceptibility" to behaviors that would lead to higher risks of head injury...Sorry about my confusion and then tangential post.

I think you and I agree that perhaps too much of the limited charitable funding pie is used to fund such genetic research efforts and too little is used to pursue non-genetics-focused efforts.

Ken Weiss said...

So the cultural issue is whether we should outlaw dangerous sports (as we do, for example, gladiator contests), or screen for some cutoff level of susceptibility to make a person eligible or not, or just allow anybody to do anything (like blood doping). Or just warn everyone.

Football can be played less violently, if as in the past there were no face-masks, etc. But should heading be outlawed in soccer? Should boxing be outlawed?

Or will we find a way to be laissez-faire, knowing that prim middle-class suburban kids will then stop playing football and soccer, and switch to something else....leaving the trauma to those with lower levels of resources and education, or who are more desperate for an economic leg up?

James Goetz said...

Hmm, I wonder if I could find a correlation between that athletic gene and brain illness? :-)