Will A Genetic Test Tell Me How Much To Exercise?

Regular readers of these pages may be well aware that there are considerable variations in how individuals respond to changes in their diets and activity levels. Some people lose weight on some diets, others don’t – some people eat less food when they exercise, others eat more.

The same applies to almost any variable that has been measured – people simply respond differently to different interventions – diet, lifestyle, medications, or even surgery.

One of the key determinants of how individuals respond, is certainly genetic. Thus, for example, a considerable body of evidence supports the notion that the response of cardiovascular risk factors like blood pressure, lipids, insulin resistance, etc. to exercise are highly heritable – in other words, some people experience significant improvements – others, performing the same amount of exercise, don’t.

So far, however, exactly which genes (let alone which variants of these genes) could determine this variability in response is largely unclear.

Nevertheless, researchers working in genetics (and the many companies involved in developing genetic tests), justify their considerable efforts with the promise of ‘personalised’ medicine, which would allow to predict disease risk and thereby allow people to adopt behaviours that could mitigate such risk (although so far there is virtually no evidence that telling people that they are at higher genetic risk for anything has any impact on their behaviours – in fact, some folks may rather take a fatalistic approach and simply decide to continue eating, drinking, and being merry).

The reason why we should probably not be holding our breath in anticipation of a genetic test that will predict who will benefit most (or least) from exercise is now outlined in an article by Jim Hagberg from the University of Maryland, published in the latest issue of the Journal of Applied Physiology.

Thus, although there is some evidence supporting “possible” candidate genes that may affect responses to exercise training – APO E and CETP for plasma lipoprotein-lipid profiles, eNOS, ACE, EDN1, and GNB3 for blood pressure, PPARG for type 2 diabetes phenotypes, and FTO and BAR genes for obesity-related phenotypes – there is one very significant barrier to advances in this field.

This limitation relates to the fact, that one would need to generate vast amounts of data from exercise interventions studies – an undertaking that may be both unfundable and unfeasible.

The need for such large sample sizes is becoming more and more evident, as attempts to find genes for diabetes, obesity or blood pressure, despite utilizing populations of 10,000 to 250,000 subjects, have found few genes that have largely minor effects – too small to have any clinical utility in predicting these conditions with any reasonable sensitivity or specificity.

As the impact of individual genes on exercise responses are likely to be of similar magnitudes, one would need to perform exercise studies in 10s of thousands of individuals to have any hope of ever finding the genetic determinants of exercise response.

This does not mean that genetics is not an important determinant of exercise response – it just means that finding the genes responsible for differences in responses is a virtually hopeless undertaking.

The same is likely true for other attempts at finding genes to predict individual responses to ‘lifestyle’ interventions.

It may well be that ‘personalised’ medicine in the future will largely be no different from ‘personalised’ medicine today, consisting namely of listening to your patients relating their personal concerns or problems and using your best judgement, your interpretation of clinical evidence (where available) and your (hopefully extensive) clinical experience to advise them the best you can.

When you think about it, it seems quite funny how the use of the term ‘personalised’ medicine in the context of genetic testing, if it ever becomes a reality, will actually result in a further ‘depersonalisation’ of medicine – sounds a lot like Orwelian Douplespeak to me.

AMS
Edmonton, Alberta

Hagberg JM (2011). Do Genetic Variations Alter the Effects of Exercise Training on Cardiovascular Disease and Can We Identify the Candidate Variants Now or In the Future? Journal of applied physiology (Bethesda, Md. : 1985) PMID: 21565989