I’m getting my DNA sequenced (part 2)

This article is the 2nd part of an article I’ve written a couple of months ago, where I have explained why I was sequencing my DNA, which you may read here. Since then, I got my results sent to me by Dante Labs, so the purpose of this 2nd article about the same topic is to explain what I’ve learned from it.

---

Practical aspects

In theory the process is very simple: you spit in a tube, send that tube by postmail to the DNA sequencing company, and then you get your results. However, in practice, things have been longer and more complicated than expected: although the sample has been sent in a timely manner, the DNA sequencing process took roughly 3 months, and needed some back and forth messaging between my assistant and Dante Labs. After months of waiting, their messages sounded pretty unconvincing and automatic, telling me that “my DNA is still being processed”.

Once I finally got the results, I got a 2nd surprise: they have indeed disclosed some results, but are asking me to pay another $199 to get the full package. I most likely will pay for these additional $199, because I’m so committed to exploring everything around longevity. If I find out meaningful things about me, interesting enough to share with you, I’ll probably post a 3rd part of this DNA sequencing series.

Overall, the customer experience has been somehow suboptimal. I’m so committed to making progress in my longevity journey, and finding as many things as possible about my body, that these minor hurdles did not stop me from doing it. However the “average” customer may be less positive, so there’s work to do in this area!

At the end of the day, knowing what is written in your genome is well worth some minor glitches!

Caveats, limitations and interpretation of the results

Before jumping into the specifics, I need to point out some facts about the results of DNA sequencing :

– your DNA is highly intricate, multifactorial and there’s much we haven’t discovered yet. Indeed there are 2 interesting notions: pleiotropy which means that a single gene codes for multiple phenotypes, and polygenic inheritance, which means that multiple genes code for the same phenotype. Well, there are plenty of those, which makes the DNA interpretation highly complex. Because of these limitations and intricacies, we just can’t be sure of what our genotype says about us.

– DNA decoding is not 100% reliable as of today. Your DNA code 3 billion base pairs long (like a very long word containing 3 billion letters among these – A, G, C, T). Because the DNA molecule is so tiny, and because of its length, there is a high likelihood of making mistakes in those 3 billion letters. Because of that, laboratories today scan it multiple times, just to make sure they haven’t made a mistake in reading some letters. My DNA has been read 30 times, but the gold standard is 100 times. Of course, the more passes you make, the more expensive it gets.

– most importantly, your DNA is NOT you. Because of the fascinating recent research in epigenetics in the last 15 years or so, we know today that whole portions of your DNA may be silenced by what is CH3 groups which stick to the portions of the DNA strand and prevent it from being expressed (so called DNA methylation). Well, depending on your environment and your lifestyle choices (the so called “exposome”), some genes will be over-expressed, and some other silenced, so having specific genes which increase the likelihood of some diseases does not mean they will necessarily be expressed.

Long story short, the results of DNA sequencing must be considered as a mere tool to add data points and fine tune your “risk profile” a little bit more, and hedge yourself against the most important risks, “just in case”. For example, having a gene that increases the risk of ASCVD (cardiovascular diseases) does not mean you’ll have it, but it may push you towards taking some more preventive measures against it, or maybe testing yourself more frequently against it, to detect it early and receive treatment against it as soon as necessary.

The results

Let me share the most salient results when it comes to my own DNA sequencing, and what actions I’m taking based on these new pieces of information.

I’ve found out a lot of good news, great genes (memory, speed of processing, etc…) but for the sake of keeping this article as short as possible, I won’t elaborate on them. Let’s just say that there are many aspects where I have very good genes (everyone has), and these areas won’t be factors of risk for me. The main focus needs to be on the higher risks, which we have to systematically mitigate :

– predisposition to weight gain (2 alleles of the FTO gene – TA and GG genotypes, both associated with weight gain and high BMI – body mass index + CT genotype of the CLOCK gene – associated with higher waist circumference). People who know me may consider this as laughable, because I’m slim, but my mom and my paternal grandmother are overweight. I mitigate this risk by practicing IR (intermittent fasing, eating 2 meals / day), roughly measuring my caloric intake (nothing extreme, but still keeping an eye on it), and regular physical activity (more or less 1h / weekday – excluded weekends when I spend time with family)

– obstructive sleep apnea (1 genotype GA of the TNF gene). Sleep apnea consists in short periods of time when you stop breathing during your sleep. This makes total sense since my father suffers from this conditions. This apparently benign condition can have serious and multiple long term effects: decrease the quality of your sleep, increase insulin resistance, and risks of cardiovascular diseases. The way I mitigate this risk is by monitoring it (my Oura ring and my Garmin watch monitor sleep apnea, but also oxygen blood saturation during sleep, which needs to be above 95% if no sleep apnea occurs). I have also learnt how to sleep in positions which do not obstruct my breathing.

– higher late onset Alzheimer’s disease (APOE genotype e3 & e4, e4 being the one which increases the risk by a factor 3 compared to the average population). Neuro-degenerative diseases are running in my family, my maternal grand-mother has dementia, so it makes totally sense that I’m exposed to it. Officially, Alzheimer’s disease has no cure as of today. However, the very last research is starting to show correlation between Alzheimer’s disease and metabolic syndrome (diabetes type 2) and arterosclerosis. Also, I’m confident that in the next 30-40 years, medicine will discover new treatments agains this disease, so I’m trying to keep myself informed about this topic.

– insulin resistance and metabolic syndrome (I have the CA genotype of the ENPP1 gene + AG genotype of the PNPLA3 gene associated with NAFLD – non alcoholic fatty liver disease). Discovering that I have this genotype was the final confirmation that I have to take aggressive preventive measures against this: wearing a CGM showed abnormal glucose levels (at the very limit between normal and abnormal values to be precise, I’ve written an article here about this), my blood tests showed the same congruent alerts (OGTT, HBA1C and fasting glucose levels). What I’m doing to mitigate this risk: I’ve stopped sugar altogether (except on trips and social events), I’ve significantly reduced my carbohydrates intake, taking measures to increase my muscle mass – because muscles absorb glucose. I’m also considering taking small quantities of metformin to further lower my glucose levels. I’ll soon write a new separate and dedicated article about this topic because it is such an important and common condition, which obviously concerns me, but may concern some of you also.

Conclusion

If you want to live more than 100 years in good health, DNA sequencing is a mandatory checkpoint. Knowing so much about yourself may seem daunting and stressful, you can choose to be ignorant, close your eyes and hope for the best. Or you can learn as much as possible about your risk factors, and aggressively hedge against these risks.

For the craziest of us, the way to mitigate those risks is not only by using DNA sequencing and all the other tools at our disposal already (as mere technology users), but also by pro-actively participating in financing and pushing anti-aging science forward (technology creators). Stay tuned, I’ll elaborate much more on this topic in the very next couple of months!