More perilous to be aware — or unaware — of your susceptibility to a disease?

Congratulations! You have welcomed a newborn. She has chubby cheeks, an adorable round tummy, and the appropriate digits. Everything appears splendid. However, unbeknownst to you, a risk lurks within her DNA: a certain percentage chance that she may develop high cholesterol and suffer a heart attack in her 40s. It could be a 5 percent possibility or perhaps even 80.

Would you wish to know?

Robert Green would. Green leads Genomes2People, a research initiative at Brigham and Women’s Hospital, the Broad Institute, and Harvard Medical School focusing on the implications of utilizing genomic data in medicine and society as a whole.

Until the advent of genomic sequencing, Green noted, transitioning from treating ill patients to practicing precision and preventative medicine was largely unfeasible.

“Genomics is somewhat at the forefront, as it allows us to profile certain vulnerabilities that a child may possess for their entire life right at birth through their DNA,” he stated. “You won’t identify every ailment; illnesses with significant environmental or lifestyle factors may evade detection. DNA isn’t a prophetic tool for every disease, yet there is a surprisingly extensive scope of human health that we can theorize about using the DNA of a newborn or a child at any stage.”

Green’s research group discovered that roughly 12 percent of infants possess a genetic mutation linked to disease. Some of these are categorized as rare diseases, but collectively, they are quite prevalent.

Holding the mutation does not guarantee the infant will contract the disease, and many conditions vary significantly regarding severity. However, Green remarked, early detection allows for regular screenings, early lifestyle modifications, or even participation in clinical trials or new cell therapies that were previously unavailable.

“Increasingly, there will be targeted genetic treatments capable of rectifying specific mutations, often before symptoms start to appear in the child,” he said. “Keep in mind, many of these characteristics could become irreversible if identified too late.”

Green himself has had his genome sequenced. He didn’t uncover anything particularly intriguing aside from being a carrier for Factor V Leiden, a mutation found in about 3 percent of individuals with European heritage. It can induce accelerated blood clotting and serves as a risk factor for developing deep vein thrombosis and pulmonary embolism. While not necessarily life-threatening, Green has still taken preventive measures based on this risk.

“I’m one of those people on long-haul flights who rises every hour to walk to the galley and perform deep knee bends,” he noted. “And I take an aspirin daily.”

For your hypothetical infant with the risk of a future heart attack, she is not alone: one in every 250 individuals carries a genetic mutation for familial hypercholesterolemia, or FH.

“From childhood through adolescence and into young adulthood, their lipid levels are significantly elevated compared to the general populace,” Green explained. “One day, a doctor might measure their cholesterol and possibly identify it, leading to treatment; however, if you have FH, early and vigorous treatment is necessary. Without it, individuals often face heart attacks or strokes by their 40s. Unfortunately, by the time many people undergo lipid testing and possibly receive treatment, it may be too late. Thus, there’s a very concrete example where we know that aggressive early management can save lives.”

The ramifications of awareness

As genomic sequencing grows more accessible, families must choose: Does the psychological weight of awareness overshadow the medical risks of ignorance?

Green and his team are astounded to find that most families opting to understand a child’s risk don’t appear to experience prolonged distress or anxiety, even upon discovering potentially severe medical threats.

“I’m not suggesting that no one feels distress,” he stated. “It’s certainly unsettling to learn that my child carries a mutation associated with cardiac risks. However, at least I’m aware of that risk and know what measures to take to monitor it.”

The widespread adoption of this preventative screening would significantly alter not only parental perspectives on their offspring but also the healthcare system, according to Green.

“If you inform that an apparently healthy child is at risk for something dire and requires surveillance, what does that imply for societal medical costs when considered across the 3.4 million infants born annually?”

The expense, he argues, is not negligible. There’s the price of genomic testing itself, which can range from $200 to $600. Moreover, there are costs associated with preventing, managing, or treating what is uncovered. For a child diagnosed with an elastin mutation, linked to supravalvular aortic stenosis, the family might incur costs of a few hundred dollars for echocardiograms every few years; conversely, if the child starts showing signs of fatigue or stunted growth, they might save money with a straightforward initial diagnostic approach.

“So…
“`

I’m not claiming that this is entirely devoid of revenue for specific healthcare expenditures, but it isn’t as severe as some individuals forecasted it would be.

Is DNA fate?

Green champions the idea that the majority of individuals would gain from genomic sequencing, yet he acknowledges the reservations of detractors. One of the primary worries, he notes, is that we aren’t equipped to handle the ambiguity of vague alterations and average probabilities.

“The strongest argument for caution is the prevailing belief that DNA is fate — the idea that if you possess a mutation, you will inevitably develop the disease — when in truth, the reality is that we are uncertain about the exact probabilities,” he stated. “We are genuinely ill-prepared to provide more detailed risk assessments.”

It can be challenging to inform a family if the likelihood of a child contracting an illness is 10 percent, 50 percent, or 75 percent. What should a parent do with a potential time bomb that may never activate?

That’s a dilemma, Green explained. “Unless you analyze a significant number of children and monitor them over time, you truly won’t be able to ascertain that information.”

Green wasn’t particularly concerned regarding data privacy issues (“Do you own a cellphone? Do you use a credit card? Do you ever search anything personal on Google? If you partake in these activities, you are far more vulnerable to privacy concerns than anything that could be derived from your genetic data”), but he mentioned that some other apprehensions are valid. “Your genetic information could be utilized for discrimination in life insurance, for instance. It’s legally permissible to do so. Although it hasn’t occurred often, it is legal.”

Nevertheless, Green believes that fears surrounding the dangers of genomics are exaggerated compared to the potential life-saving advantages.

“Once we commence sequencing children, once we start sequencing adults, your acquaintances, your neighbors, individuals in your book club, someone is going to narrate, ‘My life was saved because I discovered I had a cancer predisposition and we detected it early.’ ‘My life was preserved because I had no clue that I was an FH carrier and required more rigorous lipid management.’ When those narratives begin to emerge, I genuinely believe we will witness a realignment of the risk/benefit perspective.”