Why I’m getting my DNA sequenced (part 1)

One of the powerful aspects (the most powerful?) of Medicine 3.0 is to use top notch technologies to provide us with valuable, easily accessible, cost efficient, and precise data about our health. Among the many tools allowing us to do that, DNA sequencing is of essence. This article analyses why and how to leverage DNA sequencing to maximise your healthspan.

The (his)story of human DNA sequencing

It’s always difficult to spot the exact chain of events that lead to a scientific breakthrough. The story arguably starts back in 1953, when Crick, Watson, Franklin and Wilkins discover the DNA helix (3 of them receive the Nobel price for this incredible discovery – Crick, Watson and Wilkins). It eventually culminated with the Human Genome Project which started in 1990, and took 13 years, until 2003, when the first Human Genome was sequenced, for a whooping budget of approximately $3 billion, under the leadership of a biotech entrepreneur called Craig Venter, and announced with a lot of media hype by the then President of the United States, Bill Clinton (ahead of time in 2000, 3 years before the final confirmation).

Since then, the process of human DNA sequencing has significantly increased in quality and reliability, and decreased in cost to a couple of hundreds of dollars (see below).

Source here: https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data

This evolution opened the door to a whole universe of possibilities when it comes to Medicine 3.0 healthcare.

Why I’m getting my DNA sequenced and why you should too

Sequencing your DNA is important because it gives you insights into specific risk factors (but also eventual strengths you may have) when it comes to your long term health. You can do many things to increase the likelyhood of you living 100 years or more in good health, but there’s so much on your plate that you won’t be able to do it all (and by the way, even if you could, it may turn your life into a nightmare), so you need to prioritize & optimize your efforts, to focus on the most important aspects. Remember my previous article, the strategy here is to find the weakest aspects of your health (the limiting factors), and to work harder on these (and eventually ignore the aspects where you have a strong family history and low risk).

Here’s a non-exhaustive list of DNA genes and alleles that you want to look at (there’s many more, as you can imagine, and new ones being discovered every year, but the purpose here is just to give you some examples):

– APOE is a gene responsible for creating lipo-proteins which transport fats in your body, and it’s strongly associated with neuro-degenerative diseases There’s 4 alleles in humans, e2, e3 and e4: e2 give you low neuro-degenerative risk, e3 is neutral, and e4 is associated with the highest risk. Since you have 2 versions of the same gene (one from your mother, one from you father), you want to know what are the 2 versions you have in your body, 2 x e2 being the best, 2 x e4 being the worst. Depending on how (un)lucky you are, there’s more or less aggressive preventive measures to reduce your risk profile. If you have 2 x e2, you’d probably do nothing. If you have 2 x e4, you’d probably aggressively optimize your lipid profile (make sure you keep your lipids (LDL) as low as possible in your body).

– KLOTHO is a gene whose KL-VS variant enhances human cognition. If you have it, lucky you, you may focus on other aspect of your healthspan!

LP(a) gene is associated with artherosclerosis. This gene controls the existence and concentration of a small “add-on” for your lipoproteins, which perturbates the body’s ability to handle blood clots and blood vessels repair and maintenance. The bigger the concentration of LP(a), the higher the risk of ASCVD (atherosclerotic cardiovascular disease).

MTHFR is another gene associated with ASCVD. Depending on what alleles you have, you may be more or less exposed to this disease.

Again, there are many genes that tell you a great deal about your risk profile, and help you take informed decisions about what to focus on when it comes to healthspan optimisations. Some additional resources to read if you want to get into this rabbit hole here and here.

Practical aspects

Once you understand how important this self-discovery step is for your healthspan, you still need to get back with your feet on the ground, and find the right company to sequence your DNA, at the right price, with the right level of reliability. The latter is paramount, because your genome has around 3 billion nucleotide pairs, and a single error in decoding it may mean you taking the wrong measures to optimize your health. For this reason, DNA sequencing is being processed by reading your genome multiple times, and using advanced statistical models to make sure it provides the right data. When it comes to “DNA reads”, the golden standard as of 2023 is 100 times – this is what you would use if you have a suspicion of genetic disease. However, the “reasonable standard” as of 2023 is 30 “DNA reads”, which means that your DNA will be read 30 times to make sure it is reliable.

Following some recommendations, I wanted to try Nebula Genomics but as incredibly as it may sound, they don’t send their kits to France (but they do in virtually any other country).

I ended up working with Dante Labs. I do not have any conflict of interest regarding this company. As of now, I’m still waiting for my results to be analysed and sent back to me. I will keep you informed of the results, as soon as I receive them.

Limitations of DNA sequencing

This “breakneck paced” technological and economic evolution of the DNA sequencing has had surprising scientific consequences: initially, researchers thought that the human DNA was the ultimate book of human life, the “Holy Bible” holding all the secrets of human biology. This is what motivated the consortium of 6 countries (France, Germany, Japan, China, UK, USA) to fund the Human Genome Project, unlocking public money to fund the project.

A few years after the first human DNA was sequenced, the scientific community was to discover soon that this was only half of the story. Indeed, the genome is important – because it stores the information the ribosomes use to produce proteins in our cells) – but what is also just as important (if not even MORE IMPORTANT) is our epigenome: in order to work properly, specific and significant portions of the DNA of each cell are silenced, and do not express themselves. The epigenome describes how our genome is properly silenced, and how and what portions of our DNA is effectively expressed. Well, DNA sequencing tells us what our genome is, but it tells us NOTHING about our epigenome (but other technologies – such as methylation profiling- allow us to do this very cost-efficiently, more in a future blog post).

The takeaway

If sequencing your DNA is of essence, understanding that your life and your future is NOT your DNA is just as important! Your epigenome sits on top of your genome, and much of what is written in your genes – good or bad – can be overwritten by your epigenome, in ways that are still poorly understood today but which are determined by the 5 pillars of our playbook to live 100+ years or more in good health: nutrition, physical exercice, sleep, mental health, medication.

In fact, some studies suggest that your genome influences only 25% of how long you’re going to live, the rest of 75% being your epigenome (read more here).

Update 2023/11/02: for those who want to know more about what I discovered about myself from the results of this DNA sequencing, you can read part 2 here.

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