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By Michael White | December 1st 2008 12:14 PM | 11 comments

About Michael White

Welcome to Adaptive Complexity, where I write about genomics, systems biology, evolution, and the connection between science and literature, government, and society.

I'm a biochemist... Full Bio

More from Michael White

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Wouldn't it be great to know if your three-year-old has the potential to be a soccer star or a top marathon runner? One genetic testing company is offering to tell you just that, so that all of you obsessive, controlling parents can get your toddlers in the proper training program right from the start.

I'm sure most of you are probably cringing at the thought of using genetics to decide what sort of future you're going to push your kid into before she can even brush her own teeth. But even if you are a parent who sees nothing wrong using a little prior information to get a head start on your kid's bright athletic career, DON'T DO IT! Leaving ethical arguments aside, there are good reasons to stay away from these tests: they are not good predictors of athletic performance.

The test at issue is one for a particular version of the ACTN3 gene, which in most people produces a muscle protein. However there is a variant of the gene which fails to produce a viable protein, which we'll call the X variant. The 'normal' variant is the R variant, and since you have two copies of ACTN3 in your genome (one from each parent), you can have two X copies (XX), two R copies (RR), or you could be heterozygous and have one of each (XR).

A 2003 paper published by a University of Sydney group found that elite sprint athletes tended to have at least one copy of the R variant. They also found that more elite female sprint athletes frequently had the RX genotype, while female endurance athletes did not have the RX combination as frequently. This is a clear example of muscle gene variant having an effect on elite athletic performance.

But it's logically flawed to go from that research to a genetic test to predict whether your child will be better at football or cross-country. And yet that is exactly what one company has done, as The New York Times reports. Atlas Sports Genetics offers to test your toddler for the ACTN3 X variant. In the story, some parents are ready to jump at the chance:

"I could see how some people might think the test would pigeonhole your child into doing fewer sports or being exposed to fewer things, but I still think it’s good to match them with the right activity,” Ms. Campiglia, 36, said as she watched a toddler class at Boulder Indoor Soccer in which Noah struggled to take direction from the coach between juice and potty breaks."

“I think it would prevent a lot of parental frustration,” she said.

Atlas Sports Genetics offers the same argument:

Doing any type of performance based sport talent identification testing is very difficult below age 6 due to developmental levels of motor skills, strength and eye-hand coordination. Atlas First looks at only genetic markers, specifically the presence of ACTN3. The presence or absence of genetic markers associated with ACTN3 have been shown to have a strong correlation to the ability of the human body do well in sports that have more characteristics with Speed/ Power events (ie. Football, soccer, volleyball, basketball) vs. those that are more pre-disposed to characteristics associated with endurance sports (ie. Cycling, cross country skiing, distance running). Knowing this information may be helpful, not in eliminating choices for sport activities but adding exposure to a host of team or individual sport events that may come easier to a young athlete.

Unfortunately the test isn't going to prevent any parental frustration. Even if we make the dubious assumption that you can match your toddler with the "right activity" to maximally develop her future athletic potential, the test is useless for achieving that. In the NY Times story, the scientists interviewed were skeptical to the point of calling such genetic tests "new versions of snake oil." I agree.

The reason this test is not a good predictor of your child's athletic potential is this: the effects of almost any genetic variant you have depends on the context - dozens or possibly hundreds of other genetic variants in your genome. You may have the RX combination of ACTN3 variants, but whether you are a great sprinter almost surely depends on variants in many other genes (and of course environmental factors). With a 'bad' combination of other genes, your ACTN3 RX genotype may be meaningless, and in fact you may be a better distance runner than sprinter. The research done by the University of Sydney group showed that the RX ACTN3 genotype probably had an impact in some elite athletes, but certainly not all, and the study said nothing about those who are non-elite athletes - maybe having the ACTN3 RX combination only makes a big difference in performance at the elite level.

Let's look at the numbers from the study: 52% of the 'control', non-elite-athletic subjects were RX, 45% of elite sprinters were RX, and 45% of the endurance runners were RX. If you look at just females, the differences are more pronounced: 50% of controls were RX, compared with 57% of sprinters and 35% percent of distance runners. In males, the distribution was reversed: only 39% of sprinters were RX and 52% of distance runners were RX.

In other words, if you pick any one individual out of the study and look at that person's ACTN3 genotype, it doesn't tell you very much.

It gets worse. This effect only shows up in certain populations. Since 2003, other studies have come out on ACTN3 and athletics:

ACTN3 has no effect in this study:

"We did not find significant differences in genotype distributions among the groups except for the ACE gene -that is, lower (P<0.05) proportion of II in rowers (10.3%) than in the total subject population (22.3%). In summary, sports performance is likely polygenic with the combined effect of hundreds of genetic variants, one possibly being the ACE ID polymorphism (at least in the sports studied here) but many others remain to be identified."

It has no effect in Africans:

Our data suggest that alpha-actinin-3 deficiency is not a major influence on performance in African athletes.

No effect in South African Triatheletes:

In conclusion, the R577X polymorphism within the ACTN3 gene was not associated with ultra-endurance performance in the 2000 and 2001 South African Ironman Triathlons.

And even if you're not destined to be a great sprinter, it doesn't mean you'll be better at endurance sports:

In summary, although the alpha-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.

If you find out that your child is RX, what are you going to do? Your female child may very well have the potential to be a fantastic long-distance runner, but if you believe the results of the test, you're going to steer her in the direction of speed/power sports. Your rambunctious RX toddler may have some genetic potential to be a great wide receiver, but later he may hate football and love distance running, meaning that he'll be much more dedicated to working hard at the sport he loves, and thus more likely to excel at it.

So before you go and blow your money on a genetic test, remember that while, on average, a certain genetic variant may have a certain effect in a certain population, the chances are good it does not have that effect in you or your child. Most of the athletic traits we're interested in are probably modulated by variants of maybe dozens of genes, and the impact of any one genetic variant depends on what other variants are around.

Perhaps some day we'll be able to test for combinations of dozens of genetic variants and make better predictions about your toddler's athletic potential, if you care badly enough to know. In the mean time, you're better off taking that $149 and spending it on gymnastics or swimming lessons, or whatever activity your kid enjoys.

Comments

adaptivecomplexity's picture
Justin over at Redneck Genetics has a good explanation of this issue of going from average, population effects to making accurate predictions about an individual.

jgerke's picture
I think it's sort of like poker.  Drawing a conclusion from a single genetic test is like going all-in after seeing that your first card is an ace.  Most people would consider that foolish.  Yes, aces are more often found in winning hands, but drawing one by no means guarantees you a win.  It depends on a lot of other variables. 

The only difference is that in the human genome you have millions of cards in your hand instead of just five.

adaptivecomplexity's picture
That's an excellent analogy. I'm going to have to keep that one in mind and use it (with attribution of course). Poker is a lot easier for most people to grasp than the pitfalls of personalized medicine.

adaptivecomplexity's picture
It's easy to understand the confusion - any genetics that most people have learned is Mendelian genetics in high school. We can predict with fairly high reliability whether your child is likely to get cystic fibrosis or have blue eyes by doing genotyping a single gene. The idea of a quantitative trait influenced by many genes with varying effects is a much less familiar concept, and thus companies that should know better can take advantage of that unfamiliarity.

Steve Davis's picture
"The reason this test is not a good predictor of your child's athletic potential is this: the effects of almost any genetic variant you have depends on the context - dozens or possibly hundreds of other genetic variants in your genome... With a 'bad' combination of other genes, your ACTN3 RX genotype may be meaningless,"
Michael, this is wonderful! Can I assume from this that you have seen through gene selection and have embraced the one true faith - Group Selection?

adaptivecomplexity's picture
You don't need group selection to explain the fact that the effect of a genetic variant is dependent on the presence of other genetic variants - that can happen even with variants whose frequencies are the result of genetic drift.

I'm not criticising group selection ( I don't really have anything intelligent to say on the subject); I'm just saying that my comments weren't based on ideas about selection.

Steve Davis's picture
Michael, you might not have been intending to say anything meaningful about selection, but you stated an obvious truth that somehow eludes gene selectionists, or those pushing what they refer to as the gene's eye view of evolution. They either deliberately or unconsciously suggest that individual genes are selected, but as you pointed out this is not the case. It is groups of genes that are selected, and I would venture to suggest that it is a characteristic that is selected, that characteristic being the result of a combination of genes. Because the characteristic pertains to a group, I believe we can confidently assert that all selection is group selection. 

adaptivecomplexity's picture
I thought the debate over group selection was about selection in individual organisms vs. selection on groups of organisms. But you're right that the fitness value of a gene is dependent on its genome 'environment' - an allele is not selected for in isolation.

adaptivecomplexity's picture
You don't need selection to explain the fact that a number of genetic variants in different parts of the genome can have an impact on a variant in ACTN3. They could be variants that have reached a relatively high frequency in a population due to genetic drift, or they could simply be recently arisen rare variants that only have a fitness impact in a minor fraction of the individuals who possess those rare variants.

Steve Davis's picture
"I thought the debate over group selection was about selection in individual organisms vs. selection on groups of organisms."
There has been confusion over the exact meaning of group selection, partly because the early group selectionists pushed what has become known as naive group selection, partly because those opposed to the idea have deliberately defined it in a way that supports their case. 
As Wilson and Wilson pointed out in their paper Rethinking the Foundation of Sociobiology, so much progress has been made in recent years in uncovering empirical evidence for group selection that it's time it was redefined.
But I think they could have gone even further to reach a conclusion based on logic, that all selection is group selection.
For I believe that the role played by a gene in the selection of a characteristic would be the same as the role of an individual in the selection or survival of a society. A society is adaptable not because of the qualities of one or two or a few individuals, but because of the character of the society as a whole, because of the sum of the mix of characteristics. An individual might play a positive role, a negative role, or a neutral role, it doesn't really matter. What matters is the net outcome.

Gerhard Adam's picture

"I thought the debate over group selection was about selection in individual organisms vs. selection on groups of organisms."



The question is really what's the difference?  Despite all the focus on individual selection, the most obvious question is that since an individual must attract a mate, then by definition, no selection occurs in complete isolation.  The larger the group, the more it becomes a selection pressure on any individual selection and as a consequence begins to determine the structure of the group.



By exerting such an influence, the group itself becomes the evolving element, since no individuals that deviate from its "standard" are generally eligible to mate.  This is precisely what some of the debate is in the game theory analysis of groups, is whether a particular strategy is stable enough to be able to resist invasion by variations.



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