You have the genome sequence results in your hands

Let us suppose that you have already gone through the process and sequenced your full genome with the best quality provider (Merogenomics can help with that, it is our raison d'être). Your ordering doctor has already received the results, as quality medical testing will always involve a medical professional to request the test on your behalf; if not, be vigilant and take your time to investigate the quality of the DNA test service you are contemplating using (we can help with that too). Let us also assume that your doctor is familiar with the DNA testing results and will share that knowledge on your next appointment (you guessed it, Merogenomics can help with that too).

You now have access to your biological code of life, the DNA code (which is massive!), and its current clinical interpretation. What happens next?

What happens next depends on why you sequenced your DNA in the first place. If it is a test to collect medical information about yourself, and if we assume that you are doing it primarily to benefit yourself, then the ultimate purpose of DNA testing for health predispositions or disease diagnosis is to persuade you to change your behaviour!

We are talking about using the new knowledge granted to you from collecting your genetic health information and to consider doing the following:

• Alter your medical management
• Alter your lifestyle to help benefit any medical management changes taking place
• Consider appropriately insuring yourself to protect yourself from any negative health outcomes
• Consider the long-term legal implications

Let us go through these one by one.

This is part 1 of a 2-part series and these four points of interest will be split in half between the two posts. Follow this link for part 2 on the topics of insurance coverage and legal considerations based on DNA testing.

Medical management and DNA sequencing

The most obvious benefit of decoding your DNA is to learn about potential health problems. Take what can be learned and either apply countering measures if they are available, or screen for the potential development of the condition so that it is caught as early on as possible. Your ordering doctor will now have additional pieces of evidence, provided that the DNA test you selected is of appropriate quality for a doctor, to actually be able to do something with the results (some DNA tests might not be of this quality). Your doctor can then take your medical history as well as your family history and place that information into context of your DNA results.

Some results might require immediate action, some might require confirmatory testing to determine if the health problem is already occurring or not, and some actions will need only occasional monitoring of the situation. But the point is that now your doctor has an extremely unique tool available at her or his disposal that allows for a preventative approach to medicine, not merely just reactionary. On top of that, your genome DNA sequence is a tool that can be utilized in medicine for the duration of your life span! Why? Because the DNA code is static information. It is not a capture of a given moment in your life, as so many screening tests are in medicine, it is a source of information which you were born with and which you will die with. The only tricky part is, how much can we learn from it?

That brings us to another point, and that is that while you might need to get your DNA code obtained once in your lifetime, you will be able to interpret it as many times as you need or desire. When you get your full genome interpretation results, they are only capturing the current scientific interpretation. Depending on what is found, this might require action, or might not. But with full genome DNA sequencing, negative or a lack of results do not necessarily mean that is truly the case. Interpretation of the human genome constantly grows, and in the future we will certainly know a whole lot more. At that point we might understand information that could pertain to you that at the moment would be a total mystery, as it is not even on the radar yet. So it is worthwhile to re-interpret the genome periodically. And the fact that the genome you were born with is static, allows for you to do that for the remainder of your life.

The best approach to that is to interpret only a portion of the genome at a time as medically needed. Here comes another added benefit of having your entire full genome available to you: having the full genome means no information is lost, so in the future as we understand more, that context can always be linked back to your DNA. If there are gaps in the DNA code, it might not allow for proper interpretation in the future, such as the information that is missing could be what sheds the light on the condition.

Say you end up having neurological issues in the future. Your genome DNA data can then be looked at and analyzed only for its content that pertains to the neurological understanding of human biology. This would mean only assessing a tiny fraction of your genome at a time, and your doctors have the security of having the genetic analysis available to them in their management of your health, to either rule-out or rule-in genetic influence.

This brings us to another important point, and that is once you have your clinical interpretation of your genome, you want to make this information available to all the specialist doctors that might be treating you, whether that be neurologists, cardiologists, lung specialists, you name it! Because any of your current or future health problems could be linked to your genetics, and if they are, it could be valuable information for the doctor in terms of how treatment should be progressing.

Lifestyle changes due to DNA testing

This one in theory is a no-brainer because the lifestyle changes we are talking about are the ones that we all have heard about. These include not smoking, eating a healthy diet, and regular exercise. We all know about that, but here is the interesting part: in almost all instances, irrespective of your genetics, maintaining such favourable lifestyle habits will dramatically reduce your chances of negative outcomes. This is supported by an amazing study from a few years ago that retrospectively looked at the coronary artery disease outcomes of nearly 56,000 people over a span of nearly 20 years, and matching the likelihood of cardiac health problems based on a lifestyle. Not surprisingly, the individuals that had good lifestyles – maintaining a quality diet, not smoking, and exercising - had nearly 50% less likelihood of experiencing heart-related problems than those who did not. If there ever was one study that should convince you of exercising and eating well, this is it! Ok, maybe we will show you one more later on that is equally persuasive. But there is a remarkable additional finding.

On top of the lifestyle information, the study participants were also scored for their genetics, and marked whether they had good genes or bad genes as it related to coronary artery disease. Good genes (or rather no problematic mutations found in those genes), promoted heart health, bad genes (or rather, pathogenic mutations found in same genes), promoted heart problems. This is indeed what was observed, as the individuals with pathogenic mutations in the cardiac genes were 91% more likely to experience negative outcomes than those who did not have these mutations! But whether you had these pathogenic mutations or not, if you did lead a good quality lifestyle, you would still cut your chances of negative outcomes by nearly half, irrespective of which group you find yourself in!

This means that genetics can certainly influence outcomes, but lifestyle habits will always still play a role in addition to that, and it is worthwhile to follow a healthy lifestyle pattern.

We mentioned that these high-quality lifestyle choices should be followed in almost all instances. When it comes to genetics, the mutations can be sorted into two kinds: those that contribute to the complex trait presentation, so called because the trait is a result of dozens, if not hundreds or even thousands of mutations, each one with only tiny effect individually; and secondly, those mutations that individually lead to serious health problems. The mutations that lead to the complex input towards an outcome are very difficult to use to determine a predicted outcome. While there is a huge interest in such complex traits because we all carry some mutations that can influence our heart's performance and long-term health, at the moment, we cannot use such data with high accuracy.

Nevertheless, the study mentioned above actually used these complex trait mutations to group patients into having "good genes" or "bad genes", and were able to show that having pathogenic mutations did increase the negative outcomes. But more importantly, that these negative outcomes can be negated to a substantial degree by a quality lifestyle.

As for the mutations that lead to serious problems, the heart is no exception, and multiple genes have been identified where the presence of mutations in such genes can have serious and dangerous health implications. Usually such genes are involved in proper heart development. One such example is the MYBPC3 gene that can result in oversized muscles of the heart (hypertrophic heart), and eventually lead to sudden cardiac death. This is one of those rare instances where excessive exercise can actually be dangerous if a person is diagnosed with hypertrophic cardiomyopathy, because it places additional stress on an already overworked heart. It is these types of mutations that you would be informed about by decoding your DNA.

As previously mentioned, the healthy lifestyle included no smoking, regular exercise, and a healthy diet, as the most beneficial effects on managing chronic disease and improving general health. You can also add quality sleep to that formula.

Unfortunately, at the moment, your genetics cannot tell you much about how you are supposed to exercise or eat, with any certainty, despite the fact that this is actually a flourishing area of DNA testing due to consumer interest and the misconception about what information DNA can actually offer. This is regrettable, because it is very likely that in the future personal DNA information will include material about these topics, but currently, such tests run the risk of causing the public to lose faith in the quality of information that DNA testing can offer.

There is emerging evidence that DNA information can inform about the propensity towards strength and endurance, and there is a lot of interest in nutrigenomics, but the actual real utility has not been demonstrated. That is because it costs lots of money to perform such experiments, and the primary focus right now is to demonstrate the medical utility towards predicting health outcomes. Current DNA information related to exercise and diet are just observations that unfortunately are used by companies to peddle to the consumer as certain evidence. But we have no doubt that as more funding flows into this area, down the road the utility will indeed be demonstrated, and that diet and exercise should be as personalized based on your own genome as much as your medicine currently is.

For the moment, you are left to your own devices, but any exercise is good, and a generalized healthy diet is not hard to structure.

But these are obvious suggestions, as you do not need expensive DNA testing to know that you should be exercising and eating well. Diet in particular appears to be a dramatic contributor to unnecessary premature death in general populations. A remarkable study just came out earlier this month looking at global diet patterns and their impact on mortality, which was produced by more than 130 scientists from more than 40 countries. Such impressive collaborations are not common, and this is the most comprehensive analysis of diet effects on health ever conducted. It concluded that poor diet is the leading contributor to adult death, accounting for 22% of all death causes, due primarily to resulting cardiovascular diseases, followed by cancers, diabetes, and kidney disease. It also contributes to 16% of disability-adjusted life years (the sum of years of life lost and years lived with disability), among the adults. These are staggering figures, indicating that poor diet is a bigger contributor to one’s shortened lifespan than even smoking! What the authors conclude is to consume less salt, eat more whole grains and fruits (these account for 50% of diet-related deaths), vegetables, nuts, and omega-3 fatty acids. The other 50% of deaths were due to the high consumption of red meat, processed meats, sugar-sweetened beverages, and trans-fatty acids. Thus, if you needed a very convincing hint on how to structure your diet, here it is.

Adapted from GBD 2017 Diet Collaborators. 2019. Lancet pii: S0140-6736(19)30041-8

It might surprise you, but for certain people, DNA testing is exactly the impetus needed to alter their lifestyle. Faced with the probabilities of serious adverse health outcomes, clients who contemplate DNA sequencing to learn about their health, are forced to put the value of health in a slightly different context than we are often accustomed to think about, in terms of whether there are any genetic predispositions or uncovered diagnoses. Health problems for the majority of us do not materialize until we age, thus we inadvertently relegate health issues as something that we do not currently have to worry about. But when you consider medical DNA testing, you have to ask yourself if you want information on untreatable conditions, and the fragility of health suddenly comes into a much clearer picture. It is also because at that point, we recognize that some aspects of our health are determined by something outside of our control, the DNA code we were born with, and the only way we can do something about it, especially if unwelcome mutations are uncovered, is to change our behaviour for the better.

Whether DNA testing changes our lifestyle behaviour has been a highly contested topic in science. The verdict is still not in, as conflicting results have been presented, even when based upon the meta-analysis of many studies dedicated to the topic. One of the most comprehensive reviews on the topic suggested that the problem with studies on the effect of DNA testing on behaviour is that the participants frequently were not provided with actionable interventions to follow, which could have positively influenced such outcomes. Many of the studies conducted were based on genetic information related to complex conditions, which as we already mentioned have poor predictability. Another major problem is that these studies almost never take any validated theories on what motivates behaviour change into their study designs. One of those aspects includes the ability to control the behaviour, which might not always be available to the participant (for example, a lack of funds to afford to pursue a change, even if it is actually desired). Nevertheless, the study concluded that “ it is possible to facilitate behaviour change using genetic testing, as the catalyst” with the most promising changes appearing to be dietary.

But certain people in the population definitely do make that effort. Just one example is from an interesting study that looked at the lifestyle changes of people who received genetic results from direct-to-consumer online tests such as 23andMe, and found that 30% of the DNA test recipients increased their vegetable intake or strength exercise. This was especially observed in participants with a lower health status.

Adapted from Nielsen DE et al. 2017. BMC Med Genomics 10(1):24

The point we are trying to make here all throughout is that besides taking clinical action to either reduce the risk of a potential future health condition, such as increasing screening or undergoing prophylactic surgery, or even undergoing treatment for an already existing condition as diagnosed from your DNA, you should also alter your lifestyle choices to complement those positive health outcomes, especially in the form of nutrition. Ultimately, if you are sequencing you genome to learn more about your health, then you should maximize your chances of keeping that health in as good of shape as possible, and hopefully you will also find yourself in the group where DNA testing provided the incentive to lead a healthier lifestyle!

This is Part 1 of 2 in a series dedicated to the topic of actions to be taken after medical full genome DNA testing. Stay tuned for Part 2! As always, should you have any questions, or wish to obtain further information on this topic or any other pertaining to genome sequencing and DNA, we at Merogenomics are always here to assist you in any way we can.

Happy DNA day everyone!

This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

Products and Services Promoted by Merogenomics Inc.

Select target group for DNA testing

Healthy screening	Undiagnosed diseases	Cancer	Prenatal

Or select popular DNA test

Pharmaco-genetic gene panel	Non-invasive prenatal screening	Cancer predisposition gene panel	Full genome