DNA expert advocates mapping the genome of every child born in New Zealand – for their future health

How do we use DNA information to be healthier and live longer?

The answer is simple, according to Professor Justin M. O’Sullivan from the Liggins Institute - sequence the genomes of all children in Aotearoa/New Zealand.

Professor O’Sullivan explains the benefits of his proposal in this highlight of Auckland University's Raising the Bar Home Series.

(Webinar available soon on the RTBHE website)

Edited highlights from the discussion

How do we tap the untapped potential of our DNA to personalise your health care and extend your life? The answer is actually relatively simple, and that is that we need to change the way we think about health care. What we need to do is move from a system that tries to correct or cure a disease to a system that focused on prevention using full patient participation. How do we do that?

For many of us, it’s a bit late to make a huge difference because the diseases that are going to kill you have already started developing. You just can’t see the symptoms yet.

The answer to what we should do is sequence the genomes of all of our children. Not a representative few, not most, but all. It’s not going to help you, but it is going to help them, and I’ll explain why.

There are 60,000 children born a year in New Zealand, and 24 machines running analysis for 24 hours a day for seven days a week would do this. As a result, we’d get DNA sequences, we’d get epigenetic marks (which are the signals from the environment) from all of those individuals in one run. All 60,000 born in Aotearoa/New Zealand.

The materials to sequence these genomes would cost $60 million. By comparison, the human genome project took thirteen years and cost US$3 billion dollars to do just one individual. So we’ve moved on. Things are faster, and we can do this.

I’m not saying this is simple. There’ll be hiccups that come along the way but eventually, over the course of a couple of years, it would become business as usual. It would impact lives in ways that we have very little understanding of now. They would be very positive impacts.

Now before you say, “We can’t do that – it’s not ethical,” we’ve already run very exhaustive tests on children, such as the Guthrie test. This looks at metabolites in their blood, it’s done on all children and it helps saves thousands of kids.

Doing the DNA in the way I’m talking about now will address both common diseases – the complex ones like diabetes, cancer, Parkinson’s, Alzheimer’s – and it will also address the rare diseases that are present in our population. And this is really important because there are 7000 of them. “Well, who cares, “you might say. “7000 rare diseases? It doesn’t really matter.”

It does matter if you’re one of those people who have it. A rare disease occurs in one in every ten of us. So currently there are 400,000 – 500,000 New Zealanders who are here now who have rare diseases, many of which are undiagnosed, and some of which can be treated. But they don’t know. This is a huge burden on not only them but their whanau. Unfortunately, 50% of rare diseases impact children lot of them kill children before they reach five years of age.

Now I know that you’re probably sick to death of talking about it but we just need to talk about COVID. I call my daughter 18837 now because that’s her COVID infection number which we worked it out based on the number of infections that NZ had had until then. So 18837 got COVID after hanging out with us for a few days beforehand. On a holiday weekend, she started to show symptoms, got tested, and we all went into isolation. But nothing happened to the rest of our family.

Now we’ve all got stories like that. We all know people who have been in very close contact for long periods of time with infected people, but they still haven’t got COVID. We all recognise as well that some people show symptoms and others don’t. Some people get hospitalised and others won’t. Some people will die, and there’s no real rhyme nor reason to this as far as we can tell just by looking at people.

The information that’s hidden in our DNA can be quite helpful in understanding why some people die of COVID and some people don’t.

We’ve used this technology to understand what’s been happening during this pandemic. The information’s incredible. A single nucleotide polymorphism or SNP (pronounced ‘snip) is a variation at a single position in a DNA sequence among individuals There are 3801 SNPs that have been associated with severe responses to COVID. 3,801. If you happen to have the right combination of those variations, then you are going to be severely infected. You are going to wind up in hospital, end up on a respirator and/or die.

There are another 4734 variants which are associated with being hospitalised. You don’t necessarily wind up on a respirator or die, but you will most likely be in hospital. Now, if information in the DNA is real and it does correlate with the severity of the infection, then there should be overlap between just being hospitalised, and being on a respirator and dying. And yes, there is.

In fact, there are about 2438 SNPs that are common to both.

From your ‘50s, half of us will have at least one condition that we will get treated for on a regular basis. As you age, you will end up with most likely more than eight. Now, those conditions aren’t independent of each other – they all develop and interact together. If you have had older loved ones and they have been treated for these conditions, you will know that when they get given a drug sometimes they need another drug to balance out some other side-effect.

Drugs react differently with different conditions. That’s because the genetic and the biological basis of those diseases is intertwined, and so they work together.

We have to understand how they do so, and we can if we sequence the genomes. And that’s a really important thing because over the course of your lifetime you are going to take about 14,000 pills. That number is staggering, and it could change that if you reduce the frequency of these conditions.

You want to achieve it progressively, empowering people to change their lifestyles by telling them what their risks are.

Sequencing our children would help. By combining those changes across the genome, we can estimate the risk of developing a particular condition, like Type 1 diabetes. There are about 70 genetic variants in your genome that will predict your risk of developing it by the time you’re five.

If you know that a person has that risk of diabetes you can monitor for its onset, or treat them to prevent the development of the antibodies that destroy their pancreas. As a result, you will extend the period of their life without Type 1 diabetes. Before the development of insulin, it was a death sentence and a horrible one. Drink lots of water, starve, die.

But Type 1 diabetes is not only a disease of kids. 40% of individuals who developed it will actually present after the age of 30. Polygenic risk scores – where we take multiple little snips and we add them all together – tell us the risk of developing a condition across the course of a life. And that’s because the genetic variants that make these scores up are inherited from your parents.

There are catalogues of polygenic risk scores online, providing about 2,199 polygenic risk scores for about 538  different traits.

So think about that for a second. 538 different traits. Many of them are diseases. If you sequence the genome you can look at those scores. Right now a lot of them aren’t going to be very accurate, but the more we do it, the more accurate they get.

The sequencing done on children could predict what will happen to them over the course of their life. We could tell them, “Because you are at risk of this disease when you are 40 or 50, do these things now.” It will push that disease back. It will extend their well-being and their life.

Risk scores work. If you tell people, say, who are in the top 8% for coronary artery disease polygenic risk scores, it empowers them to change their behaviour and actually gives them more personal control, which actually reduces their overall risk.

About the speaker

Justin M. O’Sullivan is a Professor and Deputy Director of the Liggins Institute. Justin was awarded the 2010 Life Technologies Life Science Award for Emerging Excellence in Molecular Biology in New Zealand. He has published more than 110 peer-reviewed articles and holds honorary appointments at the Garvan Institute of Medical Research and the University of Southampton. Justin’s research is focused on understanding how disease-associated mutations in non-coding DNA affect gene regulatory networks and the pathways that underlie disease development. He is also investigating the role and functions of the human gut microbiome. His goal is to integrate these two fields of study.

Raising the Bar is presented in association with the University of Auckland